Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal illness characterized by progressive motor neuron degeneration. Conventional therapies for ALS are based on treatment of symptoms, and the disease remains incurable. Molecular mechanisms are unclear, but studies have been pointing to involvement of glia, neuroinflammation, oxidative stress, and glutamate excitotoxicity as a key factor. Nowadays, we have few treatments for this disease that only delays death, but also does not stop the neurodegenerative process. These treatments are based on glutamate blockage (riluzole), tyrosine kinase inhibition (masitinib), and antioxidant activity (edaravone). In the past few years, plant-derived compounds have been studied for neurodegenerative disorder therapies based on neuroprotection and glial cell response. In this review, we describe mechanisms of action of natural compounds associated with neuroprotective effects, and the possibilities for new therapeutic strategies in ALS.
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References
Abrahams S, Haylett WL, Johnson G, Carr JA, Bardien S (2019) Antioxidant effects of curcumin in models of neurodegeneration, aging, oxidative and nitrosative stress: a review. Neuroscience 406:1–21. https://doi.org/10.1016/j.neuroscience.2019.02.020
Al-Chalabi A, Hardiman O (2013) The epidemiology of ALS: a conspiracy of genes, environment and time. Nat Rev Neurol 9(11):617–628. https://doi.org/10.1038/nrneurol.2013.203
Allaman I, Bélanger M, Magistretti PJ (2011) Astrocyte-neuron metabolic relationships: for better and for worse. Trends Neurosci 34(2):76–87. https://doi.org/10.1016/j.tins.2010.12.001
Amador-Ortiz C, Lin WL, Ahmed Z, Personett D, Davies P, Duara R, Graff-Radford NR, Hutton ML, Dickson DW (2007) TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer’s disease. Ann Neurol 61(5):435–445. https://doi.org/10.1002/ana.21154
Anneser JM, Cookson MR, Ince PG, Shaw PJ, Borasio GD (2001) Glial cells of the spinal cord and subcortical white matter upregulate neuronal nitric oxide synthase in sporadic amyotrophic lateral sclerosis. Exp Neurol 171(2):418–421. https://doi.org/10.1006/exnr.2001.7756
Arai T, Mackenzie IR, Hasegawa M, Nonoka T, Niizato K, Tsuchiya K, Iritani S, Onaya M, Akiyama H (2009) Phosphorylated TDP-43 in Alzheimer’s disease and dementia with Lewy bodies. Acta Neuropathol 117(2):125–136. https://doi.org/10.1007/s00401-008-0480-1
Askarizadeh A, Barreto GE, Henney NC, Majeed M, Sahebkar A (2020) Neuroprotection by curcumin: a review on brain delivery strategies. Int J Pharm 585:119476. https://doi.org/10.1016/j.ijpharm.2020.119476
Assis LC, Straliotto MR, Engel D, Hort MA, Dutra RC, de Bem AF (2014) β-Caryophyllene protects the C6 glioma cells against glutamate-induced excitotoxicity through the Nrf2 pathway. Neuroscience 279:220–231. https://doi.org/10.1016/j.neuroscience.2014.08.043
Awano T, Johnson GS, Wade CM, Katz ML, Johnson GC, Taylor JF, Perloski M, Biagi T, Baranowska I, Long S, March PA, Olby NJ, Shelton GD, Khan S, O’Brien DP, Lindblad-Toh K, Coates JR (2009) Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A 106(8):2794–2799. https://doi.org/10.1073/pnas.0812297106
Ayala YM, Zago P, D’Ambrogio A, Xu YF, Petrucelli L, Buratti E, Baralle FE (2008) Structural determinants of the cellular localization and shuttling of TDP-43. J Cell Sci 121(Pt 22):3778–3785. https://doi.org/10.1242/jcs.038950
Aydin E, Türkez H, Taşdemir S (2013) Anticancer and antioxidant properties of terpinolene in rat brain cells. Arh Hig Rada Toksikol 64(3):415–424. https://doi.org/10.2478/10004-1254-64-2013-2365
Badshah H, Ali T, Rehman S-U, Amin F-U, Ullah F, Kim TH, Kim MO (2016) Protective effect of lupeol against lipopolysaccharide-induced neuroinflammation via the p38/c-Jun N-terminal kinase pathway in the adult mouse brain. J Neuroimmune Pharmacol 11(1):48–60. https://doi.org/10.1007/s11481-015-9623-z
Barbeito LH, Pehar M, Cassina P, Vargas MR, Peluffo H, Viera L, Estévez AG, Beckman JS (2004) A role for astrocytes in motor neuron loss in amyotrophic lateral sclerosis. Brain Res Brain Res Rev 47(1–3):263–274. https://doi.org/10.1016/j.brainresrev.2004.05.003
Baron EP (2018) Medicinal properties of cannabinoids, terpenes, and flavonoids in cannabis, and benefits in migraine, headache, and pain: an update on current evidence and cannabis science. Headache 58(7):1139–1186. https://doi.org/10.1111/head.13345
Bendotti C, Tortarolo M, Suchak SK, Calvaresi N, Carvelli L, Bastone A, Rizzi M, Rattray M, Mennini T (2001) Transgenic SOD1 G93A mice develop reduced GLT-1 in spinal cord without alterations in cerebrospinal fluid glutamate levels. J Neurochem 79(4):737–746. https://doi.org/10.1046/j.1471-4159.2001.00572.x
Bhatia NK, Modi P, Sharma S, Deep S (2020) Quercetin and baicalein act as potent antiamyloidogenic and fibril destabilizing agents for SOD1 fibrils. ACS Chem Neurosci 11(8):1129–1138. https://doi.org/10.1021/acschemneuro.9b00677
Bhatia NK, Srivastava A, Katyal N, Jain N, Khan MA, Kundu B (1854) Deep S (2015) Curcumin binds to the pre-fibrillar aggregates of Cu/Zn superoxide dismutase (SOD1) and alters its amyloidogenic pathway resulting in reduced cytotoxicity. Biochim Biophys Acta 5:426–436. https://doi.org/10.1016/j.bbapap.2015.01.014
Blokhuis AM, Groen EJ, Koppers M, van den Berg LH, Pasterkamp RJ (2013) Protein aggregation in amyotrophic lateral sclerosis. Acta Neuropathol 125(6):777–794. https://doi.org/10.1007/s00401-013-1125-6
Bonesi M, Menichini F, Tundis R, Loizzo MR, Conforti F, Passalacqua NG, Statti GA (2010) Acetylcholinesterase and butyrylcholinesterase inhibitory activity of Pinus species essential oils and their constituents. J Enzyme Inhib Med Chem 25(5):622–628. https://doi.org/10.3109/14756360903389856
Bruijn LI, Becher MW, Lee MK, Anderson KL, Jenkins NA, Copeland NG, Sisodia SS, Rothstein JD, Borchelt DR, Price DL, Cleveland DW (1997) ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions. Neuron 18(2):327–338. https://doi.org/10.1016/s0896-6273(00)80272-x
Bruijn LI, Miller TM, Cleveland DW (2004) Unraveling the mechanisms involved in motor neuron degeneration in ALS. Annu Rev Neurosci 27:723–749. https://doi.org/10.1146/annurev.neuro.27.070203.144244
Buratti E, Baralle FE (2008) Multiple roles of TDP-43 in gene expression, splicing regulation, and human disease. Front Biosci 13:867–878. https://doi.org/10.2741/2727
Carriedo SG, Yin HZ, Weiss JH (1996) Motor neurons are selectively vulnerable to AMPA/kainate receptor-mediated injury in vitro. J Neurosci 16(13):4069–4079
Chen D, Zhang X-Y, Sun J, Cong Q-J, Chen W-X, Ahsan HM, Gao J, Qian J-J (2019) Asiatic acid protects dopaminergic neurons from neuroinflammation by suppressing mitochondrial ROS production. Biomol Ther 27(5):442–449. https://doi.org/10.4062/biomolther.2018.188
Chen LW, Horng LY, Wu CL, Sung HC, Wu RT (2012) Activating mitochondrial regulator PGC-1α expression by astrocytic NGF is a therapeutic strategy for Huntington’s disease. Neuropharmacology 63(4):719–732. https://doi.org/10.1016/j.neuropharm.2012.05.019
Chen X, Tansey MG (2011) The role of neuroinflammation in Parkinson’s disease. In: Neuroinflammation. Elsevier, pp 403–421
Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, Ko JY, Lin JT, Lin BR, Ming-Shiang W, Yu HS, Jee SH, Chen GS, Chen TM, Chen CA, Lai MK, Pu YS, Pan MH, Wang YJ et al (2001) Phase I clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 21(4b):2895–2900
Corcia P, Pradat PF, Salachas F, Bruneteau G, Forestier N, Seilhean D, Hauw JJ, Meininger V (2008) Causes of death in a postmortem series of ALS patients. Amyotroph Lateral Scler 9(1):59–62. https://doi.org/10.1080/17482960701656940
Costa SL, Silva VDA, dos Santos SC, Santos CC, Paris I, Muñoz P, Segura-Aguilar J (2016) Impact of plant-derived flavonoids on neurodegenerative diseases. Neurotox Res 30(1):41–52. https://doi.org/10.1007/s12640-016-9600-1
Coyle JT, Puttfarcken P (1993) Oxidative stress, glutamate, and neurodegenerative disorders. Science 262(5134):689–695. https://doi.org/10.1126/science.7901908
Cozzolino M, Carrì MT (2012) Mitochondrial dysfunction in ALS. Prog Neurobiol 97(2):54–66. https://doi.org/10.1016/j.pneurobio.2011.06.003
Cruz-Correa M, Hylind LM, Marrero JH, Zahurak ML, Murray-Stewart T, Casero RA Jr, Montgomery EA, Iacobuzio-Donahue C, Brosens LA, Offerhaus GJ, Umar A, Rodriguez LM, Giardiello FM (2018) Efficacy and safety of curcumin in treatment of intestinal adenomas in patients with familial adenomatous polyposis. Gastroenterology 155(3):668–673. https://doi.org/10.1053/j.gastro.2018.05.031
Dajas F, Rivera-Megret F, Blasina F, Arredondo F, Abin-Carriquiry JA, Costa G, Echeverry C, Lafon L, Heizen H, Ferreira M, Morquio A (2003) Neuroprotection by flavonoids. Braz J Med Biol Res 36(12):1613–1620. https://doi.org/10.1590/s0100-879x2003001200002
Dende C, Meena J, Nagarajan P, Nagaraj VA, Panda AK, Padmanaban G (2017) Nanocurcumin is superior to native curcumin in preventing degenerative changes in experimental cerebral malaria. Sci Rep 7(1):10062. https://doi.org/10.1038/s41598-017-10672-9
Díaz-Amarilla P, Olivera-Bravo S, Trias E, Cragnolini A, Martínez-Palma L, Cassina P, Beckman J, Barbeito L (2011) Phenotypically aberrant astrocytes that promote motoneuron damage in a model of inherited amyotrophic lateral sclerosis. Proc Natl Acad Sci USA 108(44):18126–18131. https://doi.org/10.1073/pnas.1110689108
Dong H, Xu L, Wu L, Wang X, Duan W, Li H, Li C (2014) Curcumin abolishes mutant TDP-43 induced excitability in a motoneuron-like cellular model of ALS. Neuroscience 272:141–153. https://doi.org/10.1016/j.neuroscience.2014.04.032
Duan W, Guo Y, Xiao J, Chen X, Li Z, Han H, Li C (2014) Neuroprotection by monocarbonyl dimethoxycurcumin C:ameliorating the toxicity of mutant TDP-43 via HO-1. Mol Neurobiol 49(1):368–379. https://doi.org/10.1007/s12035-013-8525-4
Elliott JL (1999) Experimental models of amyotrophic lateral sclerosis. Neurobiol Dis 6(5):310–320. https://doi.org/10.1006/nbdi.1999.0266
Estes PS, Boehringer A, Zwick R, Tang JE, Grigsby B, Zarnescu DC (2011) Wild-type and A315T mutant TDP-43 exert differential neurotoxicity in a Drosophila model of ALS. Hum Mol Genet 20(12):2308–2321. https://doi.org/10.1093/hmg/ddr124
Ferraiuolo L, Higginbottom A, Heath PR, Barber S, Greenald D, Kirby J, Shaw PJ (2011) Dysregulation of astrocyte-motoneuron cross-talk in mutant superoxide dismutase 1-related amyotrophic lateral sclerosis. Brain 134(Pt 9):2627–2641. https://doi.org/10.1093/brain/awr193
Fischer LR, Culver DG, Tennant P, Davis AA, Wang M, Castellano-Sanchez A, Khan J, Polak MA, Glass JD (2004) Amyotrophic lateral sclerosis is a distal axonopathy: evidence in mice and man. Exp Neurol 185(2):232–240. https://doi.org/10.1016/j.expneurol.2003.10.004
Flora G, Gupta D, Tiwari A (2013) Nanocurcumin: a promising therapeutic advancement over native curcumin. Crit Rev Ther Drug Carrier Syst 30(4):331–368. https://doi.org/10.1615/critrevtherdrugcarriersyst.2013007236
Foran E, Bogush A, Goffredo M, Roncaglia P, Gustincich S, Pasinelli P, Trotti D (2011) Motor neuron impairment mediated by a sumoylated fragment of the glial glutamate transporter EAAT2. Glia 59(11):1719–1731. https://doi.org/10.1002/glia.21218
Freibaum BD, Lu Y, Lopez-Gonzalez R, Kim NC, Almeida S, Lee KH, Badders N, Valentine M, Miller BL, Wong PC, Petrucelli L, Kim HJ, Gao FB, Taylor JP (2015) GGGGCC repeat expansion in C9orf72 compromises nucleocytoplasmic transport. Nature 525(7567):129–133. https://doi.org/10.1038/nature14974
Frey D, Schneider C, Xu L, Borg J, Spooren W, Caroni P (2000) Early and selective loss of neuromuscular synapse subtypes with low sprouting competence in motoneuron diseases. J Neurosci 20(7):2534–2542. https://doi.org/10.1523/jneurosci.20-07-02534.2000
Gertsch J, Leonti M, Raduner S, Racz I, Chen J-Z, Xie X-Q, Altmann K-H, Karsak M, Zimmer A (2008) Beta-caryophyllene is a dietary cannabinoid. Proc Natl Acad Sci 105(26):9099. https://doi.org/10.1073/pnas.0803601105
González-Cofrade L, de Las HB, Apaza Ticona L, Palomino OM (2019) Molecular targets involved in the neuroprotection mediated by terpenoids. Planta Med 85(17):1304–1315. https://doi.org/10.1055/a-0953-6738
Gowing G, Philips T, Van Wijmeersch B, Audet JN, Dewil M, Van Den Bosch L, Billiau AD, Robberecht W, Julien JP (2008) Ablation of proliferating microglia does not affect motor neuron degeneration in amyotrophic lateral sclerosis caused by mutant superoxide dismutase. J Neurosci 28(41):10234–10244. https://doi.org/10.1523/jneurosci.3494-08.2008
Grosskreutz J, Van Den Bosch L, Keller BU (2010) Calcium dysregulation in amyotrophic lateral sclerosis. Cell Calcium 47(2):165–174. https://doi.org/10.1016/j.ceca.2009.12.002
Guimarães AG, Serafini MR, Quintans-Júnior LJ (2014) Terpenes and derivatives as a new perspective for pain treatment: a patent review. Expert Opin Ther Pat 24(3):243–265. https://doi.org/10.1517/13543776.2014.870154
Gurney ME, Pu H, Chiu AY, Dal Canto MC, Polchow CY, Alexander DD, Caliendo J, Hentati A, Kwon YW, Deng HX (1994) Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation. Science 264(5166):1772–1775. https://doi.org/10.1126/science.8209258
Haastert K, Grosskreutz J, Jaeckel M, Laderer C, Bufler J, Grothe C, Claus P (2005) Rat embryonic motoneurons in long-term coculture with Schwann cells–a system to investigate motoneuron diseases on a cellular level in vitro. J Neurosci Methods 142(2):275–284. https://doi.org/10.1016/j.jneumeth.2004.09.003
Han S, Choi JR, Soon Shin K, Kang SJ (2012) Resveratrol upregulated heat shock proteins and extended the survival of G93ASOD1 mice. Brain Res 1483:112–117. https://doi.org/10.1016/j.brainres.2012.09.022
Hasselmo ME, Giocomo LM (2006) Cholinergic modulation of cortical function. J Mol Neurosci 30(1–2):133–135. https://doi.org/10.1385/jmn:30:1:133
Hendriks JJ, de Vries HE, van der Pol SM, van den Berg TK, van Tol EA, Dijkstra CD (2003) Flavonoids inhibit myelin phagocytosis by macrophages, a structure-activity relationship study. Biochem Pharmacol 65(5):877–885. https://doi.org/10.1016/s0006-2952(02)01609-x
Hensley K, Abdel-Moaty H, Hunter J, Mhatre M, Mou S, Nguyen K, Potapova T, Pye Q, Qi M, Rice H, Stewart C, Stroukoff K, West M (2006) Primary glia expressing the G93A-SOD1 mutation present a neuroinflammatory phenotype and provide a cellular system for studies of glial inflammation. J Neuroinflammation 3(1):2. https://doi.org/10.1186/1742-2094-3-2
West M (2006) Primary glia expressing the G93A-SOD1 mutation present a neuroinflammatory phenotype and provide a cellular system for studies of glial inflammation. J Neuroinflammation 3(1):2. https://doi.org/10.1186/1742-2094-3-2
Hickman S, Izzy S, Sen P, Morsett L, El Khoury J (2018) Microglia in neurodegeneration. Nat Neurosci 21(10):1359–1369. https://doi.org/10.1038/s41593-018-0242-x
Higashi S, Iseki E, Yamamoto R, Minegishi M, Hino H, Fujisawa K, Togo T, Katsuse O, Uchikado H, Furukawa Y, Kosaka K, Arai H (2007) Concurrence of TDP-43, tau and alpha-synuclein pathology in brains of Alzheimer’s disease and dementia with Lewy bodies. Brain Res 1184:284–294. https://doi.org/10.1016/j.brainres.2007.09.048
Huang L, Guan T, Qian Y, Huang M, Tang X, Li Y, Sun H (2011) Anti-inflammatory effects of maslinic acid, a natural triterpene, in cultured cortical astrocytes via suppression of nuclear factor-kappa B. Eur J Pharmacol 672(1–3):169–174. https://doi.org/10.1016/j.ejphar.2011.09.175
Ip P, Sharda PR, Cunningham A, Chakrabartty S, Pande V, Chakrabartty A (2017) Quercitrin and quercetin 3-β-d-glucoside as chemical chaperones for the A4V SOD1 ALS-causing mutant. Protein Eng Des Sel 30(6):431–440. https://doi.org/10.1093/protein/gzx025
Irrera N, D'Ascola A, Pallio G, Bitto A, Mannino F, Arcoraci V, Rottura M, Ieni A, Minutoli L, Metro D, Vaccaro M, Altavilla D, Squadrito F (2020) β-Caryophyllene inhibits cell proliferation through a direct modulation of CB2 receptors in glioblastoma cells. Cancers (Basel) 12(4). https://doi.org/10.3390/cancers12041038
Isaac JT, Ashby MC, McBain CJ (2007) The role of the GluR2 subunit in AMPA receptor function and synaptic plasticity. Neuron 54(6):859–871. https://doi.org/10.1016/j.neuron.2007.06.001
Ji RR, Suter MR (2007) p38 MAPK, microglial signaling, and neuropathic pain. Mol Pain 3:33. https://doi.org/10.1186/1744-8069-3-33
Jiang H, Tian X, Guo Y, Duan W, Bu H, Li C (2011) Activation of nuclear factor erythroid 2-related factor 2 cytoprotective signaling by curcumin protect primary spinal cord astrocytes against oxidative toxicity. Biol Pharm Bull 34(8):1194–1197. https://doi.org/10.1248/bpb.34.1194
Jiang W, Li M, He F, Bian Z, He Q, Wang X, Yao W, Zhu L (2016) Neuroprotective effect of asiatic acid against spinal cord injury in rats. Life Sci 157:45–51. https://doi.org/10.1016/j.lfs.2016.05.004
Joyce PI, McGoldrick P, Saccon RA, Weber W, Fratta P, West SJ, Zhu N, Carter S, Phatak V, Stewart M, Simon M, Kumar S, Heise I, Bros-Facer V, Dick J, Corrochano S, Stanford MJ, Luong TV, Nolan PM et al (2015) A novel SOD1-ALS mutation separates central and peripheral effects of mutant SOD1 toxicity. Hum Mol Genet 24(7):1883–1897. https://doi.org/10.1093/hmg/ddu605
Kamata H, Manabe T, Oka S, Kamata K, Hirata H (2002) Hydrogen peroxide activates IkappaB kinases through phosphorylation of serine residues in the activation loops. FEBS Lett 519(1–3):231–237. https://doi.org/10.1016/s0014-5793(02)02712-6
Karlstetter M, Lippe E, Walczak Y, Moehle C, Aslanidis A, Mirza M, Langmann T (2011) Curcumin is a potent modulator of microglial gene expression and migration. J Neuroinflammation 8:125. https://doi.org/10.1186/1742-2094-8-125
Kennel PF, Finiels F, Revah F, Mallet J (1996) Neuromuscular function impairment is not caused by motor neurone loss in FALS mice: an electromyographic study. NeuroReport 7(8):1427–1431. https://doi.org/10.1097/00001756-199605310-00021
Kim D, Nguyen MD, Dobbin MM, Fischer A, Sananbenesi F, Rodgers JT, Delalle I, Baur JA, Sui G, Armour SM, Puigserver P, Sinclair DA, Tsai LH (2007) SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer’s disease and amyotrophic lateral sclerosis. EMBO J 26(13):3169–3179. https://doi.org/10.1038/sj.emboj.7601758
King AE, Woodhouse A, Kirkcaldie MT, Vickers JC (2016) Excitotoxicity in ALS: overstimulation, or overreaction? Exp Neurol 275(Pt 1):162–171. https://doi.org/10.1016/j.expneurol.2015.09.019
Koh SH, Lee SM, Kim HY, Lee KY, Lee YJ, Kim HT, Kim J, Kim MH, Hwang MS, Song C, Yang KW, Lee KW, Kim SH, Kim OH (2006) The effect of epigallocatechin gallate on suppressing disease progression of ALS model mice. Neurosci Lett 395(2):103–107. https://doi.org/10.1016/j.neulet.2005.10.056
Koza LA, Winter AN, Holsopple J, Baybayon-Grandgeorge AN, Pena C, Olson JR, Mazzarino RC, Patterson D, Linseman DA (2020) Protocatechuic acid extends survival, improves motor function, diminishes gliosis, and sustains neuromuscular junctions in the HSOD1g93a mouse model of amyotrophic lateral sclerosis. Nutrients 12(6):1–26. https://doi.org/10.3390/nu12061824
Kunze A, Lengacher S, Dirren E, Aebischer P, Magistretti PJ, Renaud P (2013) Astrocyte-neuron co-culture on microchips based on the model of SOD mutation to mimic ALS. Integr Biol (Camb) 5(7):964–975. https://doi.org/10.1039/c3ib40022k
Lee M, Hyun D, Jenner P, Halliwell B (2001) Effect of overexpression of wild-type and mutant Cu/Zn-superoxide dismutases on oxidative damage and antioxidant defences: relevance to Down’s syndrome and familial amyotrophic lateral sclerosis. J Neurochem 76(4):957–965. https://doi.org/10.1046/j.1471-4159.2001.00107.x
Lemmens R, Van Hoecke A, Hersmus N, Geelen V, D’Hollander I, Thijs V, Van Den Bosch L, Carmeliet P, Robberecht W (2007) Overexpression of mutant superoxide dismutase 1 causes a motor axonopathy in the zebrafish. Hum Mol Genet 16(19):2359–2365. https://doi.org/10.1093/hmg/ddm193
Levites Y, Weinreb O, Maor G, Youdim MB, Mandel S (2001) Green tea polyphenol (-)-epigallocatechin-3-gallate prevents Nmethyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration. J Neurochem 78(5):1073–1082. https://doi.org/10.1046/j.1471-4159.2001.00490.x
Li FQ, Wang T, Pei Z, Liu B, Hong JS (2005) Inhibition of microglial activation by the herbal flavonoid baicalein attenuates inflammation-mediated degeneration of dopaminergic neurons. J Neural Transm (Vienna) 112(3):331–347. https://doi.org/10.1007/s00702-004-0213-0
Liao B, Zhao W, Beers DR, Henkel JS, Appel SH (2012) Transformation from a neuroprotective to a neurotoxic microglial phenotype in a mouse model of ALS. Exp Neurol 237(1):147–152. https://doi.org/10.1016/j.expneurol.2012.06.011
Liu J, Wang F (2017) Role of neuroinflammation in amyotrophic lateral sclerosis: cellular mechanisms and therapeutic implications. Front Immunol 8:1005. https://doi.org/10.3389/fimmu.2017.01005
Liu Y, Pattamatta A, Zu T, Reid T, Bardhi O, Borchelt DR, Yachnis AT, Ranum LP (2016) C9orf72 BAC mouse model with motor deficits and neurodegenerative features of ALS/FTD. Neuron 90(3):521–534. https://doi.org/10.1016/j.neuron.2016.04.005
Lu J, Duan W, Guo Y, Jiang H, Li Z, Huang J, Hong K, Li C (2012) Mitochondrial dysfunction in human TDP-43 transfected NSC34 cell lines and the protective effect of dimethoxy curcumin. Brain Res Bull 89(5–6):185–190. https://doi.org/10.1016/j.brainresbull.2012.09.005
Luft R (1994) The development of mitochondrial medicine. Proc Natl Acad Sci USA 91(19):8731–8738. https://doi.org/10.1073/pnas.91.19.8731
Madeswaran A, Umamaheswari M, Asokkumar K, Sivashanmugam T, Subhadradevi V, Jagannath P (2012) In silico docking studies of aldose reductase inhibitory activity of commercially available flavonoids. Bangladesh J Pharmacol 7(4):266–271
Maihöfner C, Probst-Cousin S, Bergmann M, Neuhuber W, Neundörfer B, Heuss D (2003) Expression and localization of cyclooxygenase-1 and -2 in human sporadic amyotrophic lateral sclerosis. Eur J Neurosci 18(6):1527–1534. https://doi.org/10.1046/j.1460-9568.2003.02879.x
Mancuso R, del Valle J, Modol L, Martinez A, Granado-Serrano AB, Ramirez-Núñez O, Pallás M, Portero-Otin M, Osta R, Navarro X (2014) Resveratrol improves motoneuron function and extends survival in SOD1G93A ALS mice. Neurotherapeutics 11(2):419–432. https://doi.org/10.1007/s13311-013-0253-y
Marchetto MC, Muotri AR, Mu Y, Smith AM, Cezar GG, Gage FH (2008) Non-cell-autonomous effect of human SOD1 G37R astrocytes on motor neurons derived from human embryonic stem cells. Cell Stem Cell 3(6):649–657. https://doi.org/10.1016/j.stem.2008.10.001
Metodiewa D, Kochman A, Karolczak S (1997) Evidence for antiradical and antioxidant properties of four biologically active N, N-diethylaminoethyl ethers of flavanone oximes: a comparison with natural polyphenolic flavonoid (rutin) action. Biochem Mol Biol Int 41(5):1067–1075. https://doi.org/10.1080/15216549700202141
Meyer K, Ferraiuolo L, Miranda CJ, Likhite S, McElroy S, Renusch S, Ditsworth D, Lagier-Tourenne C, Smith RA, Ravits J, Burghes AH, Shaw PJ, Cleveland DW, Kolb SJ, Kaspar BK (2014) Direct conversion of patient fibroblasts demonstrates non-cell autonomous toxicity of astrocytes to motor neurons in familial and sporadic ALS. Proc Natl Acad Sci 111(2):829. https://doi.org/10.1073/pnas.1314085111
Miller R, Mitchell J, Lyon M, Moore D (2002a) Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). In: Miller R (ed) Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd. https://doi.org/10.1002/14651858.CD001447
Mizielinska S, Grönke S, Niccoli T, Ridler CE, Clayton EL, Devoy A, Moens T, Norona FE, Woollacott IOC, Pietrzyk J, Cleverley K, Nicoll AJ, Pickering-Brown S, Dols J, Cabecinha M, Hendrich O, Fratta P, Fisher EMC, Partridge L, Isaacs AM (2014) C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins. Science 345(6201):1192–1194. https://doi.org/10.1126/science.1256800
Mulder DW, Kurland LT, Offord KP, Beard CM (1986) Familial adult motor neuron disease: amyotrophic lateral sclerosis. Neurology 36(4):511–517. https://doi.org/10.1212/wnl.36.4.511
Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417(1):1–13. https://doi.org/10.1042/BJ20081386
Nagai M, Re DB, Nagata T, Chalazonitis A, Jessell TM, Wichterle H, Przedborski S (2007) Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons. Nat Neurosci 10(5):615–622. https://doi.org/10.1038/nn1876
Neumann M, Sampathu DM, Kwong LK, Truax AC, Micsenyi MC, Chou TT, Bruce J, Schuck T, Grossman M, Clark CM, McCluskey LF, Miller BL, Masliah E, Mackenzie IR, Feldman H, Feiden W, Kretzschmar HA, Trojanowski JQ, Lee VM (2006) Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314(5796):130–133. https://doi.org/10.1126/science.1134108
Neymotin A, Calingasan NY, Wille E, Naseri N, Petri S, Damiano M, Liby KT, Risingsong R, Sporn M, Beal MF, Kiaei M (2011) Neuroprotective effect of Nrf2/ARE activators, CDDO ethylamide and CDDO trifluoroethylamide, in a mouse model of amyotrophic lateral sclerosis. Free Radic Biol Med 51(1):88–96. https://doi.org/10.1016/j.freeradbiomed.2011.03.027
Ogawa M, Shidara H, Oka K, Kurosawa M, Nukina N, Furukawa Y (2015) Cysteine residues in Cu, Zn-superoxide dismutase are essential to toxicity in Caenorhabditis elegans model of amyotrophic lateral sclerosis. Biochem Biophys Res Commun 463(4):1196–1202. https://doi.org/10.1016/j.bbrc.2015.06.084
Okle O, Stemmer K, Deschl U, Dietrich DR (2013) L-BMAA induced ER stress and enhanced caspase 12 cleavage in humanneuroblastoma SH-SY5Y cells at low nonexcitotoxic concentrations. Toxicol Sci 131(1):217–224. https://doi.org/10.1093/toxsci/kfs291
Oliveira-Junior MS, Pereira EP, de Amorim VCM, Reis LTC, do Nascimento RP, da Silva VDA, Costa SL (2019) Lupeol inhibits LPS-induced neuroinflammation in cerebellar cultures and induces neuroprotection associated to the modulation of astrocyte response and expression of neurotrophic and inflammatory factors. Int Immunopharmacol 70:302–312. https://doi.org/10.1016/j.intimp.2019.02.055
Paduch R, Kandefer-Szerszeń M, Trytek M, Fiedurek J (2007) Terpenes: substances useful in human healthcare. Arch Immunol Ther Exp (warsz) 55(5):315–327. https://doi.org/10.1007/s00005-007-0039-1
Pakdeechote P, Bunbupha S, Kukongviriyapan U, Prachaney P, Khrisanapant W, Kukongviriyapan V (2014) Asiatic acid alleviates hemodynamic and metabolic alterations via restoring eNOS/iNOS expression, oxidative stress, and inflammation in diet induced metabolic syndrome rats. Nutrients 6(1):355–370
Panche AN, Diwan AD, Chandra SR (2016) Flavonoids: an overview. J Nutr Sci 5:e47. https://doi.org/10.1017/jns.2016.41
Papadeas ST, Kraig SE, O’Banion C, Lepore AC, Maragakis NJ (2011) Astrocytes carrying the superoxide dismutase 1 (SOD1G93A) mutation induce wild-type motor neuron degeneration in vivo. Proc Natl Acad Sci U S A 108(43):17803–17808. https://doi.org/10.1073/pnas.1103141108
Parmar SK, Sharma TP, Airao VB, Bhatt R, Aghara R, Chavda S, Rabadiya SO, Gangwal A (2013) Neuropharmacological effects of triterpenoids. In: In, vol 4. Phytopharmacology, pp 354–372
Pasinelli P, Brown RH (2006) Molecular biology of amyotrophic lateral sclerosis: insights from genetics. Nat Rev Neurosci 7(9):710–723. https://doi.org/10.1038/nrn1971
Pellerin L, Magistretti PJ (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci USA 91(22):10625–10629. https://doi.org/10.1073/pnas.91.22.10625
Picher-Martel V, Valdmanis PN, Gould PV, Julien JP, Dupré N (2016) From animal models to human disease: a genetic approach for personalized medicine in ALS. Acta Neuropathol Commun 4(1):70. https://doi.org/10.1186/s40478-016-0340-5
Pinto S, Cunha C, Barbosa M, Vaz AR, Brites D (2017) Exosomes from NSC-34 cells transfected with hSOD1-G93A are enriched in miR-124 and drive alterations in microglia phenotype. Front Neurosci 11:273. https://doi.org/10.3389/fnins.2017.00273
Qian K, Huang H, Peterson A, Hu B, Maragakis NJ, Ming GL, Chen H, Zhang SC (2017) Sporadic ALS astrocytes induce neuronal degeneration in vivo. Stem Cell Reports 8(4):843–855. https://doi.org/10.1016/j.stemcr.2017.03.003
Qian Y, Guan T, Tang X, Huang L, Huang M, Li Y, Sun H (2011) Maslinic acid, a natural triterpenoid compound from Olea europaea, protects cortical neurons against oxygen–glucose deprivation-induced injury. Eur J Pharmacol 670(1):148–153
Qian Y, Huang M, Guan T, Chen L, Cao L, Han XJ, Huang L, Tang X, Li Y, Sun H (2015) Maslinic acid promotes synaptogenesis and axon growth via Akt/GSK-3β activation in cerebral ischemia model. Eur J Pharmacol 764:298–305. https://doi.org/10.1016/j.ejphar.2015.07.028
Qian Y, Xin Z, Lv Y, Wang Z, Zuo L, Huang X, Li Y, Xin HB (2018) Asiatic acid suppresses neuroinflammation in BV2 microglia via modulation of the Sirt1/NF-κB signaling pathway. Food Funct 9(2):1048–1057. https://doi.org/10.1039/C7FO01442B
Qin S, Huang L, Gong J, Shen S, Huang J, Ren H, Hu H (2017) Efficacy and safety of turmeric and curcumin in lowering blood lipid levels in patients with cardiovascular risk factors: a meta-analysis of randomized controlled trials. Nutr J 16(1):68. https://doi.org/10.1186/s12937-017-0293-y
Qu Z, Zheng N, Wei Y, Chen Y, Zhang Y, Zhang M, Chang H, Liu J, Ai H, Geng X, Wang Q, Yin L (2019) Effect of cornel iridoid glycoside on microglia activation through suppression of the JAK/STAT signalling pathway. J Neuroimmunol 330. https://doi.org/10.1016/j.jneuroim.2019.01.014
Ramesh T, Lyon AN, Pineda RH, Wang C, Janssen PM, Canan BD, Burghes AH, Beattie CE (2010) A genetic model of amyotrophic lateral sclerosis in zebrafish displays phenotypic hallmarks of motoneuron disease. Dis Model Mech 3(9–10):652–662. https://doi.org/10.1242/dmm.005538
Ransom BR, Neale E, Henkart M, Bullock PN, Nelson PG (1977) Mouse spinal cord in cell culture. I. Morphology and intrinsic neuronal electrophysiologic properties. J Neurophysiol 40(5):1132–1150. https://doi.org/10.1152/jn.1977.40.5.1132
Rao SD, Yin HZ, Weiss JH (2003) Disruption of glial glutamate transport by reactive oxygen species produced in motor neurons. J Neurosci 23(7):2627–2633
Reynolds A, Laurie C, Mosley RL, Gendelman HE (2007) Oxidative stress and the pathogenesis of neurodegenerative disorders. Int Rev Neurobiol 82:297–325. https://doi.org/10.1016/s0074-7742(07)82016-2
Rix Brooks B, Berry JD, Ciepielewska M, Liu Y, Zambrano GS, Zhang J, Hagan M (2022) Intravenous edaravone treatment in ALS and survival: an exploratory, retrospective, administrative claims analysis. EClinicalMedicine 52:101590. https://doi.org/10.1016/j.eclinm.2022.101590
Rizzuto R, De Stefani D, Raffaello A, Mammucari C (2012) Mitochondria as sensors and regulators of calcium signalling. Nat Rev Mol Cell Biol 13(9):566–578. https://doi.org/10.1038/nrm3412
Rodrigues MC, Voltarelli JC, Sanberg PR, Borlongan CV, Garbuzova-Davis S (2012) Immunological aspects in amyotrophic lateral sclerosis. Transl Stroke Res 3(3):331–340. https://doi.org/10.1007/s12975-012-0177-6
Rouault TA, Tong WH (2005) Iron-sulphur cluster biogenesis and mitochondrial iron homeostasis. Nat Rev Mol Cell Biol 6(4):345–351. https://doi.org/10.1038/nrm1620
Rowland LP, Shneider NA (2001) Amyotrophic lateral sclerosis. N Engl J Med 344(22):1688–1700. https://doi.org/10.1056/NEJM200105313442207
Zarei S, Carr K, Reiley L, Diaz K, Guerra O, Altamirano PF, Pagani W, Lodin D, Orozco G, Chinea A (2015) A comprehensive review of amyotrophic lateral sclerosis. Surg Neurol Int 6. https://doi.org/10.4103/2152-7806.169561
Scheffler IE (2011) Mitochondria. J. W. Sons, Ed. 2 edn.
Schroeter H, Boyd C, Spencer JP, Williams RJ, Cadenas E, Rice-Evans C (2002) MAPK signaling in neurodegeneration:influences of flavonoids and of nitric oxide. Neurobiol Aging 23(5):861–880. https://doi.org/10.1016/s0197-4580(02)00075-1
Scott A (2017) Drug therapy: on the treatment trail for ALS. Nature 550(7676):S120–S121. https://doi.org/10.1038/550S120a
Sebastià J, Kieran D, Breen B, King MA, Netteland DF, Joyce D, Fitzpatrick SF, Taylor CT, Prehn JH (2009) Angiogenin protects motoneurons against hypoxic injury. Cell Death Differ 16(9):1238–1247. https://doi.org/10.1038/cdd.2009.52
Segat GC, Manjavachi MN, Matias DO, Passos GF, Freitas CS, Costa R, Calixto JB (2017) Antiallodynic effect of β-caryophyllene on paclitaxel-induced peripheral neuropathy in mice. Neuropharmacology 125:207–219. https://doi.org/10.1016/j.neuropharm.2017.07.015
Seo J-S, Choi J, Leem Y-H, Han P-L (2015) Rosmarinic acid alleviates neurological symptoms in the G93A-SOD1 transgenic mouse model of amyotrophic lateral sclerosis. Exp Neurobiol 24(4):341–350. https://doi.org/10.5607/en.2015.24.4.341
Sharifi-Rad M, Nv AK, Zucca P, Varoni EM, Dini L, Panzarini E, Rajkovic J, Tsouh Fokou PV, Azzini E, Peluso I, Prakash Mishra A, Nigam M, el Rayess Y, Mel B, Polito L, Iriti M, Martins N, Martorell M, Docea AO, Sharifi-Rad J (2020a) Lifestyle, oxidative stress, and antioxidants: back and forth in the pathophysiology of chronic diseases. In: Frontiers in physiology, vol 11. Frontiers Media S.A. https://doi.org/10.3389/fphys.2020a.00694
Sharifi-Rad M, Lankatillake C, Dias DA, Docea AO, Mahomoodally MF, Lobine D, Chazot PL, Kurt B, Tumer TB, Moreira AC, Sharopov F, Martorell M, Martins N, Cho WC, Calina D, Sharifi-Rad J (2020b) Impact of natural compounds on neurodegenerative disorders: from preclinical to pharmacotherapeutics. J Clin Med 9(4):MDPI. https://doi.org/10.3390/jcm9041061
Sharma RA, McLelland HR, Hill KA, Ireson CR, Euden SA, Manson MM, Pirmohamed M, Marnett LJ, Gescher AJ, Steward WP (2001) Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer. Clin Cancer Res 7(7):1894–1900
Shimojo Y, Kosaka K, Noda Y, Shimizu T, Shirasawa T (2010) Effect of rosmarinic acid in motor dysfunction and life span in a mouse model of familial amyotrophic lateral sclerosis. J Neurosci Res 88(4):896–904. https://doi.org/10.1002/jnr.22242
Simon A, Allais DP, Duroux JL, Basly JP, Durand-Fontanier S, Delage C (1998) Inhibitory effect of curcuminoids on MCF-7 cell proliferation and structure-activity relationships. Cancer Lett 129(1):111–116. https://doi.org/10.1016/s0304-3835(98)00092-5
Simpson EP, Yen AA, Appel SH (2003) Oxidative stress: a common denominator in the pathogenesis of amyotrophic lateral sclerosis. Curr Opin Rheumatol 15(6):730–736. https://doi.org/10.1097/00002281-200311000-00008
Solanki I, Parihar P, Mansuri ML, Parihar MS (2015) Flavonoid-based therapies in the early management of neurodegenerative diseases. Adv Nutr 6(1):64–72. https://doi.org/10.3945/an.114.007500
Soo KY, Atkin JD, Horne MK, Nagley P (2009) Recruitment of mitochondria into apoptotic signaling correlates with the presence of inclusions formed by amyotrophic lateral sclerosis-associated SOD1 mutations. J Neurochem 108(3):578–590. https://doi.org/10.1111/j.1471-4159.2008.05799.x
Srinivasan E, Rajasekaran R (2016) Computational investigation of curcumin, a natural polyphenol that inhibits the destabilization and the aggregation of human SOD1 mutant (Ala4Val). RSC Adv 6(104):102744–102753
Srinivasan E, Rajasekaran R (2017) Probing the inhibitory activity of epigallocatechin-gallate on toxic aggregates of mutant (L84F) SOD1 protein through geometry based sampling and steered molecular dynamics. J Mol Graph Model 74:288–295. https://doi.org/10.1016/j.jmgm.2017.04.019
Srinivasan E, Rajasekaran R (2018) Comparative binding of kaempferol and kaempferide on inhibiting the aggregate formation of mutant (G85R) SOD1 protein in familial amyotrophic lateral sclerosis: a quantum chemical and molecular mechanics study. BioFactors 44(5):431–442. https://doi.org/10.1002/biof.1441
Srinivasan E, Rajasekaran R (2019) Molecular binding response of naringin and naringenin to H46R mutant SOD1 protein in combating protein aggregation using density functional theory and discrete molecular dynamics. Prog Biophys Mol Biol 145:40–51. https://doi.org/10.1016/j.pbiomolbio.2018.12.003
Stratoulias V, Venero JL, Tremblay M, Joseph B (2019a) Microglial subtypes: diversity within the microglial community. EMBO J 38(17):e101997. https://doi.org/10.15252/embj.2019a101997
Stratoulias V, Venero JL, Tremblay M, Joseph B (2019b) Microglial subtypes: diversity within the microglial community. EMBO J 38(17). https://doi.org/10.15252/embj.2019b101997
Tafuri F, Ronchi D, Magri F, Comi GP, Corti S (2015) SOD1 misplacing and mitochondrial dysfunction in amyotrophic lateral sclerosis pathogenesis. Front Cell Neurosci 9:336. https://doi.org/10.3389/fncel.2015.00336
Tan W, Pasinelli P, Trotti D (2014) Role of mitochondria in mutant SOD1 linked amyotrophic lateral sclerosis. Biochim Biophys Acta 1842(8):1295–1301. https://doi.org/10.1016/j.bbadis.2014.02.009
Taylor JP, Brown RH Jr, Cleveland DW (2016) Decoding ALS: from genes to mechanism. Nature 539(7628):197–206. https://doi.org/10.1038/nature20413
Tetali SD (2019) Terpenes and isoprenoids: a wealth of compounds for global use. Planta 249(1):1–8. https://doi.org/10.1007/s00425-018-3056-x
Tortelli R, Copetti M, Panza F, Fontana A, Cortese R, Capozzo R, Introna A, D’Errico E, Zoccolella S, Arcuti S, Seripa D, Simone IL, Logroscino G (2016) Time to generalization and prediction of survival in patients with amyotrophic lateral sclerosis: a retrospective observational study. Eur J Neurol 23(6):1117–1125. https://doi.org/10.1111/ene.12994
Tovar-Y-Romo LB, Santa-Cruz LD, Zepeda A, Tapia R (2009) Chronic elevation of extracellular glutamate due to transport blockade is innocuous for spinal motoneurons in vivo. Neurochem Int 54(3–4):186–191. https://doi.org/10.1016/j.neuint.2008.09.015
Trias E, Ibarburu S, Barreto-Núñez R, Barbeito L (2017) Significance of aberrant glial cell phenotypes in pathophysiology of amyotrophic lateral sclerosis. Neurosci Lett 636:27–31. https://doi.org/10.1016/j.neulet.2016.07.052
Trias E, King PH, Si Y, Kwon Y, Varela V, Ibarburu S, Kovacs M, Moura IC, Beckman JS, Hermine O, Barbeito L (2018) Mast cells and neutrophils mediate peripheral motor pathway degeneration in ALS. JCI Insight 3(19). https://doi.org/10.1172/jci.insight.123249
Tsao S-M, Yin M-C (2015) Antioxidative and antiinflammatory activities of asiatic acid, glycyrrhizic acid, and oleanolic acid in human bronchial epithelial cells. J Agric Food Chem 63(12):3196–3204. https://doi.org/10.1021/acs.jafc.5b00102
Veyrat-Durebex C, Corcia P, Dangoumau A, Laumonnier F, Piver E, Gordon PH, Andres CR, Vourc’h P, Blasco H (2014) Advances in cellular models to explore the pathophysiology of amyotrophic lateral sclerosis. Mol Neurobiol 49(2):966–983. https://doi.org/10.1007/s12035-013-8573-9
Vijayakumar UG, Milla V, Stafford MYC, Bjourson AJ, Duddy W, Duguez SMR (2019) A systematic review of suggested molecular strata, biomarkers and their tissue sources in ALS. Front Neurol 10. https://doi.org/10.3389/fneur.2019.00400
Volkening K, Leystra-Lantz C, Yang W, Jaffee H, Strong MJ (2009) Tar DNA binding protein of 43 kDa (TDP-43), 14–3-3 proteins and copper/zinc superoxide dismutase (SOD1) interact to modulate NFL mRNA stability. Implications for altered RNA processing in amyotrophic lateral sclerosis (ALS). Brain Res 1305:168–182. https://doi.org/10.1016/j.brainres.2009.09.105
Volonté C, Apolloni S, Parisi C, Amadio S (2016) Purinergic contribution to amyotrophic lateral sclerosis. Neuropharmacology 104:180–193. https://doi.org/10.1016/j.neuropharm.2015.10.026
Walker EH, Pacold ME, Perisic O, Stephens L, Hawkins PT, Wymann MP, Williams RL (2000) Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Mol Cell 6(4):909–919. https://doi.org/10.1016/s1097-2765(05)00089-4
Wang J, Zhang Y, Tang L, Zhang N, Fan D (2011a) Protective effects of resveratrol through the up-regulation of SIRT1 expression in the mutant hSOD1-G93A-bearing motor neuron-like cell culture model of amyotrophic lateral sclerosis. Neurosci Lett 503(3):250–255. https://doi.org/10.1016/j.neulet.2011.08.047
Wang L, Gutmann DH, Roos RP (2011b) Astrocyte loss of mutant SOD1 delays ALS disease onset and progression in G85R transgenic mice. Hum Mol Genet 20(2):286–293. https://doi.org/10.1093/hmg/ddq463
Wang W, Wang L, Lu J, Siedlak SL, Fujioka H, Liang J, Jiang S, Ma X, Jiang Z, da Rocha EL, Sheng M, Choi H, Lerou PH, Li H, Wang X (2016) The inhibition of TDP-43 mitochondrial localization blocks its neuronal toxicity. Nat Med 22(8):869–878. https://doi.org/10.1038/nm.4130
Watson MR, Lagow RD, Xu K, Zhang B, Bonini NM (2008) A drosophila model for amyotrophic lateral sclerosis reveals motor neuron damage by human SOD1. J Biol Chem 283(36):24972–24981. https://doi.org/10.1074/jbc.M804817200
Wegorzewska I, Bell S, Cairns NJ, Miller TM, Baloh RH (2009) TDP-43 mutant transgenic mice develop features of ALS and frontotemporal lobar degeneration. Proc Natl Acad Sci USA 106(44):18809–18814. https://doi.org/10.1073/pnas.0908767106
Winter AN, Ross EK, Wilkins HM, Stankiewicz TR, Wallace T, Miller K, Linseman DA (2018) An anthocyanin-enriched extract from strawberries delays disease onset and extends survival in the hSOD1G93A mouse model of amyotrophic lateral sclerosis. Nutr Neurosci 21(6):414–426. https://doi.org/10.1080/1028415X.2017.1297023
Wong PC, Pardo CA, Borchelt DR, Lee MK, Copeland NG, Jenkins NA, Sisodia SS, Cleveland DW, Price DL (1995) An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria. Neuron 14(6):1105–1116. https://doi.org/10.1016/0896-6273(95)90259-7
Wu CS, Chen YJ, Chen JJ, Shieh JJ, Huang CH, Lin PS, Chang GC, Chang JT, Lin CC (2012) Terpinen-4-ol induces apoptosis in human nonsmall cell lung cancer in vitro and in vivo. Evid Based Complement Alternat Med 2012:818261. https://doi.org/10.1155/2012/818261
Xu R, Wu C, Zhang X, Zhang Q, Yang Y, Yi J, Yang R, Tao Y (2011) Linking hypoxic and oxidative insults to cell death mechanisms in models of ALS. Brain Res 1372:133–144. https://doi.org/10.1016/j.brainres.2010.11.056
Xu Z, Chen S, Li X, Luo G, Li L, Le W (2006) Neuroprotective effects of (-)-epigallocatechin-3-gallate in a transgenic mouse model of amyotrophic lateral sclerosis. Neurochem Res 31(10):1263–1269. https://doi.org/10.1007/s11064-006-9166-z
Xu Z, Poidevin M, Li X, Li Y, Shu L, Nelson DL, Li H, Hales CM, Gearing M, Wingo TS, Jin P (2013) Expanded GGGGCC repeat RNA associated with amyotrophic lateral sclerosis and frontotemporal dementia causes neurodegeneration. Proc Natl Acad
Sci U S A 110(19):7778–7783. https://doi.org/10.1073/pnas.1219643110
Ya BL, Li CY, Zhang L, Wang W, Li L (2010) Cornel iridoid glycoside inhibits inflammation and apoptosis in brains of rats with focal cerebral ischemia. Neurochem Res 35(5):773–781. https://doi.org/10.1007/s11064-010-0134-2
Yang H, Wang G, Sun H, Shu R, Liu T, Wang CE, Liu Z, Zhao Y, Zhao B, Ouyang Z, Yang D, Huang J, Zhou Y, Li S, Jiang X, Xiao Z, Li XJ, Lai L (2014) Species-dependent neuropathology in transgenic SOD1 pigs. Cell Res 24(4):464–481. https://doi.org/10.1038/cr.2014.25
Yodkeeree S, Chaiwangyen W, Garbisa S, Limtrakul P (2009) Curcumin, demethoxycurcumin and bisdemethoxycurcumin differentially inhibit cancer cell invasion through the down-regulation of MMPs and uPA. J Nutr Biochem 20(2):87–95. https://doi.org/10.1016/j.jnutbio.2007.12.003
Yoo KY, Park SY (2012) Terpenoids as potential anti-Alzheimer’s disease therapeutics. Molecules 17(3):3524–3538. https://doi.org/10.3390/molecules17033524
Yu J, Jia Y, Guo Y, Chang G, Duan W, Sun M, Li B, Li C (2010) Epigallocatechin-3-gallate protects motor neurons and regulates glutamate level. FEBS Lett 584(13):2921–2925. https://doi.org/10.1016/j.febslet.2010.05.011
Zachariah TJ, Leela NK (2015) Curcumin or curcumnoids: industrial and medicinal potential.
Zhao W, Beers DR, Henkel JS, Zhang W, Urushitani M, Julien JP, Appel SH (2010) Extracellular mutant SOD1 induces microglial-mediated motoneuron injury. Glia 58(2):231–243. https://doi.org/10.1002/glia.20919
Zheng T, Peng J, Pei T, Shi Y, Liu L, Chen K, Xiao H, Chen Y (2019) Cornel iridoid glycoside exerts a neuroprotective effect on neuroinflammation in rats with brain injury by inhibiting NF-κB and STAT3. 3. Biotech 9(5). https://doi.org/10.1007/s13205-019-1697-5
Ahmadi, M., Agah, E., Nafissi, S., Jaafari, M. R., Harirchian, M. H., Sarraf, P., Faghihi-kashani, S., Hosseini, S. J., Ghoreishi, A., & Aghamollaii, V. (2018). Safety and efficacy of nanocurcumin as add-on therapy to riluzole in patients with amyotrophic lateral sclerosis : A pilot randomized clinical trial.
Albani D, Polito L, Signorini A, Forloni G (2010) Neuroprotective properties of resveratrol in different neurodegenerative disorders. BioFactors 36(5):370–376. https://doi.org/10.1002/biof.118
Annunziata F, Pinna C, Dallavalle S, Tamborini L, Pinto A (2020) An overview of coumarin as a versatile and readily accessible scaffold with broad-ranging biological activities. Int J Mol Sci 21(13):4618. https://doi.org/10.3390/ijms21134618
Ash PEA, Bieniek KF, Gendron TF, Caulfield T, Lin W-L, DeJesus-Hernandez M, van Blitterswijk MM, Jansen-West K, Paul JW, Rademakers R, Boylan KB, Dickson DW, Petrucelli L (2013) Unconventional translation of C9ORF72 GGGGCC expansion generates insoluble polypeptides specific to c9FTD/ALS. Neuron 77(4):639–646. https://doi.org/10.1016/j.neuron.2013.02.004
Balendra R, Isaacs AM (2018) C9orf72-mediated ALS and FTD: multiple pathways to disease. Nat Rev Neurol 14(9):544–558. https://doi.org/10.1038/s41582-018-0047-2
Barber SC, Higginbottom A, Mead RJ, Barber S, Shaw PJ (2009) An in vitro screening cascade to identify neuroprotective antioxidants in ALS. Free Radic Biol Med 46(8):1127–1138. https://doi.org/10.1016/j.freeradbiomed.2009.01.019
Batra R, Lee CW (2017) Mouse models of C9orf72 hexanucleotide repeat expansion in amyotrophic lateral sclerosis/frontotemporal dementia. Front Cell Neurosci 11:196
Chico L, Ienco EC, Bisordi C, Lo Gerfo A, Petrozzi L, Petrucci A, Mancuso M, Siciliano G (2018) Amyotrophic lateral sclerosis and oxidative stress: a double-blind therapeutic trial after curcumin supplementation. CNS Neurol Disord - Drug Targets 17(10):767–779. https://doi.org/10.2174/1871527317666180720162029
Cunha-Oliveira T, Montezinho L, Mendes C, Firuzi O, Saso L, Oliveira PJ, Silva FSG (2020) Oxidative stress in amyotrophic lateral sclerosis: pathophysiology and opportunities for pharmacological intervention. In: Oxidative medicine and cellular longevity, vol 2020, Hindawi Limited. https://doi.org/10.1155/2020/5021694
da Silva AB, Cerqueira Coelho PL, das Neves Oliveira M, Oliveira JL, Oliveira Amparo JA, da Silva KC, Costa SL (2020) The flavonoid rutin and its aglycone quercetin modulate the microglia inflammatory profile improving antiglioma activity. Brain Behav Immun 85:170–185. https://doi.org/10.1016/j.bbi.2019.05.003
Dai H, Huang M, Qian J, Liu J, Meng C, Li Y, Ling Y (2019) Excellent antitumor and antimetastatic activities based on novel coumarin/pyrazole oxime hybrids. Eur J Med Chem 166:470–479. https://doi.org/10.1016/j.ejmech.2019.01.070
Duan W, Guo Y, Xiao J, Chen X (2013) Neuroprotection by monocarbonyl dimethoxycurcumin C : Ameliorating the toxicity of mutant TDP-43 via HO-1. https://doi.org/10.1007/s12035-013-8525-4
El Khawand, T., Courtois, A., Valls, J., Richard, T., & Krisa, S. (2018). A review of dietary stilbenes: sources and bioavailability. In Phytochem Rev (Vol. 17, Issue 5, pp. 1007–1029). Springer Netherlands. https://doi.org/10.1007/s11101-018-9578-9
Feng D, Zhang A, Yang Y, Yang P (2020) Coumarin-containing hybrids and their antibacterial activities. Arch Pharm (Weinheim) 353(6):e1900380. https://doi.org/10.1002/ardp.201900380
Fitzgerald KC, O’Reilly ÉJ, Fondell E, Falcone GJ, McCullough ML, Park Y, Kolonel LN, Ascherio A (2013) Intakes of vitamin C and carotenoids and risk of amyotrophic lateral sclerosis: Pooled results from 5 cohort studies. Ann Neurol 73(2):236–245. https://doi.org/10.1002/ana.23820
Fonteles AA, de Souza CM, de Sousa Neves JC, Menezes APF, Santos do Carmo MR, Fernandes FDP, de Araújo PR, de Andrade GM (2016) Rosmarinic acid prevents against memory deficits in ischemic mice. Behav Brain Res 297:91–103. https://doi.org/10.1016/j.bbr.2015.09.029
Fylaktakidou KC, Hadjipavlou-Litina DJ, Litinas KE, Nicolaides DN (2004) Natural and synthetic coumarin derivatives with anti-inflammatory/ antioxidant activities. Curr Pharm Des 10(30):3813–3833. https://doi.org/10.2174/1381612043382710
Gao M, Liu N, Li XM, Chao LW, Lin HQ, Wang Y, Sun Y, Huang C, Li XG, Deng M (2021) Epidemiology and factors predicting survival of amyotrophic lateral sclerosis in a large Chinese cohort. Chin Med J 134(18):2231–2236. https://doi.org/10.1097/CM9.0000000000001679
Hassan MZ, Osman H, Ali MA, Ahsan MJ (2016) Therapeutic potential of coumarins as antiviral agents. Eur J Med Chem 123:236–255. https://doi.org/10.1016/j.ejmech.2016.07.056
Isonaka R, Hiruma H, Katakura T, Kawakami T (2011) Inhibition of superoxide dismutase selectively suppresses growth of rat spinal motor neurons: Comparison with phosphorylated neurofilament-containing spinal neurons. Brain Research 1425:13–19. https://doi.org/10.1016/j.brainres.2011.09.046
Isonaka R, Katakura T, Kawakami T (2012) Effect of inhibition of superoxide dismutase on motor neurons during growth: Comparison of phosphorylated and non-phosphorylated neurofilament- containing spinal neurons by histogram distribution. Brain Research 1470:11–16. https://doi.org/10.1016/j.brainres.2012.06.014
Jameel E, Umar T, Kumar J, Hoda N (2016) Coumarin: A Privileged Scaffold for the Design and Development of Antineurodegenerative Agents. Chem Biol Drug Des 87(1):21–38. https://doi.org/10.1111/cbdd.12629
Jennum P, Ibsen R, Pedersen SW, Kjellberg J (2013) Mortality, health, social and economic consequences of amyotrophic lateral sclerosis: a controlled national study. Journal of Neurology 260(3):785–793. https://doi.org/10.1007/s00415-012-6706-0
Koh SH, Kwon H, Kim KS, Kim J, Kim MH, Yu HJ, Kim M, Lee KW, Do BR, Jung HK, Yang KW, Appel SH, Kim SH (2004) Epigallocatechin gallate prevents oxidative-stress-induced death of mutant Cu/Zn-superoxide dismutase (G93A) motoneuron cells by alteration of cell survival and death signals. Toxicology 202(3):213–225. https://doi.org/10.1016/j.tox.2004.05.008
Korkmaz OT, Aytan N, Carreras I, Choi JK, Kowall NW, Jenkins BG, Dedeoglu A (2014) 7,8-Dihydroxyflavone improves motor performance and enhances lower motor neuronal survival in a mouse model of amyotrophic lateral sclerosis. Neuroscience Letters 566:286–291. https://doi.org/10.1016/j.neulet.2014.02.058
Kumar N, Goel N (2019) Phenolic acids: Natural versatile molecules with promising therapeutic applications. In: Biotechnology reports, vol 24. Elsevier B.V. https://doi.org/10.1016/j.btre.2019.e00370
Kuršvietienė, L., Stanevičienė, I., Mongirdienė, A., & Bernatonienė, J. (2016). Multiplicity of effects and health benefits of resveratrol. In Medicina (Lithuania) (Vol. 52, Issue 3, pp. 148–155). Elsevier B.V. https://doi.org/10.1016/j.medici.2016.03.003
Lei L, Xue YB, Liu Z, Peng SS, He Y, Zhang Y, Zhang YH (2015) Coumarin derivatives from Ainsliaea fragrans and their anticoagulant activity. Sci Rep 5:13544. https://doi.org/10.1038/srep13544
Manochkumar J, Doss CGP, El-Seedi HR, Efferth T, Ramamoorthy S (2021) The neuroprotective potential of carotenoids in vitro and in vivo. Phytomedicine : International Journal of Phytotherapy and Phytopharmacology 91:153676. https://doi.org/10.1016/j.phymed.2021.15367
Mathew B, Parambi DGT, Mathew GE, Uddin MS, Inasu ST, Kim H, Carradori S (2019) Emerging therapeutic potentials of dual-acting MAO and AChE inhibitors in Alzheimer's and Parkinson's diseases. Arch Pharm (Weinheim) 352(11):e1900177. https://doi.org/10.1002/ardp.201900177
Miller R, Mitchell J, Lyon M, Moore D (2002b) Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). In: Miller R (ed) Cochrane database of systematic reviews. John Wiley & Sons, Ltd. https://doi.org/10.1002/14651858.CD001447 -> É outra referencia, de 2012
Mori K, Weng S-M, Arzberger T, May S, Rentzsch K, Kremmer E, Schmid B, Kretzschmar HA, Cruts M, van Broeckhoven C, Haass C, Edbauer D (2013) The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD/ALS. Science 339(6125):1335–1338. https://doi.org/10.1126/science.1232927
Nakamura M, Suzuki T, Takagi M, Tamura H, Masuda T (2014) Stimulation of phosphorylation of ERK and CREB by phellopterin and auraptene isolated from Citrus junos. Nat Prod Commun 9(10):1934578X1400901021
Namitha KK, Negi PS (2010) Chemistry and biotechnology of carotenoids. Crit Rev Food Sci Nutr 50(8):728–760. https://doi.org/10.1080/10408398.2010.499811
Orhan IE, Gulcan HO (2015) Coumarins: auspicious cholinesterase and monoamine oxidase inhibitors. Curr Top Med Chem 15(17):1673–1682. https://doi.org/10.2174/1568026615666150427113103
Park SJ, Ahmad F, Philp A, Baar K, Williams T, Luo H, Ke H, Rehmann H, Taussig R, Brown AL, Kim MK, Beaven MA, Burgin AB, Manganiello V, Chung JH (2012) Resveratrol ameliorates aging related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell 148(3):421–433. https://doi.org/10.1016/j.cell.2012.01.017
Pereira EPL, Braga-De-Souza S, Santos CC, Santos LO, Cerqueira MD, Ribeiro PR, Fernandez LG, Silva VDA, Costa SL (2017) Amburana cearensis seed extracts protect PC-12 cells against toxicity induced by glutamate. Revista Brasileira de Farmacognosia 27(2):199–205. https://doi.org/10.1016/j.bjp.2016.08.010
Pereira TM, Franco DP, Vitorio F, Kummerle AE (2018) Coumarin compounds in medicinal chemistry: some important examples from the last years. Curr Top Med Chem 18(2):124–148. https://doi.org/10.2174/1568026618666180329115523
Prakash A, Kumar A (2014) Implicating the role of lycopene in restoration of mitochondrial enzymes and BDNF levels in β-amyloid induced Alzheimers disease. Eur J Pharmacoly 741:104–111. https://doi.org/10.1016/j.ejphar.2014.07.036
Pupillo E, Messina P, Logroscino G, Beghi E, Micheli A, Rosettani P, Baldini D, Bianchi G, Rigamonti A, Bonito V, Chiveri L, Guidotti M, Rezzonico M, Vidale S, Corbo M, Lunetta C, Maestri E, Cotelli MS, Filosto M, Mazzini L (2014) Long-term survival in amyotrophic lateral sclerosis: A population-based study. Ann Neurol 75(2):287–297. https://doi.org/10.1002/ana.24096
Qin HL, Zhang ZW, Ravindar L, Rakesh KP (2020) Antibacterial activities with the structure-activity relationship of coumarin derivatives. Eur J Med Chem 207:112832. https://doi.org/10.1016/j.ejmech.2020.112832
Rashmi HB, Negi PS (2020) Phenolic acids from vegetables: A review on processing stability and health benefits. In: Food Research International, vol 136, Elsevier Ltd. https://doi.org/10.1016/j.foodres.2020.109298
Rodríguez-Enríquez F, Costas-Lago MC, Besada P, Alonso-Pena M, Torres-Terán I, Viña D, Terán C (2020) Novel coumarin-pyridazine hybrids as selective MAO-B inhibitors for the Parkinson's disease therapy. Bioorg Chem 104:104203. https://doi.org/10.1016/j.bioorg.2020.104203
Sachdeva AK, Chopra K (2015) Lycopene abrogates Aβ(1-42)-mediated neuroinflammatory cascade in an experimental model of Alzheimer’s disease. J Nutr Biochem 26(7):736–744. https://doi.org/10.1016/j.jnutbio.2015.01.012
Shang AJ, Yang Y, Wang HY, Tao BZ, Wang J, Wang ZF, Zhou DB (2017) Spinal cord injury effectively ameliorated by neuroprotective effects of rosmarinic acid. Nutritional Neuroscience 20(3):172–179. https://doi.org/10.1080/1028415X.2015.1103460
Shaw PJ, Ince PG, Falkous G, Mantle D (1995) Oxidative damage to protein in sporadic motor neuron disease spinal cord. Ann Neurol 38(4):691–695. https://doi.org/10.1002/ana.410380424
Song XF, Fan J, Liu L, Liu XF, Gao F (2020) Coumarin derivatives with anticancer activities: An update. Arch Pharm (Weinheim) 353(8):e2000025. https://doi.org/10.1002/ardp.202000025
Tafesse TB, Bule MH, Khoobi M, Faramarzi MA, Abdollahi M, Amini M (2020) Coumarin-based scaffold as α-glucosidase inhibitory activity: implication for the development of potent antidiabetic agents. Mini Rev Med Chem 20(2):134-151. https://doi.org/10.2174/1389557519666190925162536
Tao D, Wang Y, Bao XQ, Yang BB, Gao F, Wang L, Li L (2019) Discovery of coumarin Mannich base derivatives as multifunctional agents against monoamine oxidase B and neuroinflammation for the treatment of Parkinson's disease. Eur J Med Chem 173:203–212. https://doi.org/10.1016/j.ejmech.2019.04.016
Thomas V, Giles D, Basavarajaswamy GPM, Das AK, Patel A (2017) Coumarin derivatives as antiinflammatory and anticancer agents. Anticancer Agents Med Chem 17(3):415–423. https://doi.org/10.2174/1871520616666160902094739
Trieu VN, Uckun FM (1999) Genistein is neuroprotective in murine models of familial amyotrophic lateral sclerosis and stroke. Biochem Biophys Res Commun 258(3):685–688. https://doi.org/10.1006/bbrc.1999.0577
Ueda T, Inden M, Shirai K, Sekine SI, Masaki Y, Kurita H, Ichihara K, Inuzuka T, Hozumi I (2017) The effects of Brazilian green propolis that contains flavonols against mutant copper-zinc superoxide dismutasemediated toxicity. Sci Rep 7(1):1–11. https://doi.org/10.1038/s41598-017-03115-y
Viña D, Matos MJ, Yáñez M, Santana L, Uriarte E (2012) 3-Substituted coumarins as dual inhibitors of AChE and MAO for the treatment of Alzheimer's disease. MedChemComm 3(2):213–218
Wang TH, Wang SY, Wang XD, Jiang HQ, Yang YQ, Wang Y, Cheng JL, Zhang CT, Liang WW, Feng HL (2018) Fisetin exerts antioxidant and neuroprotective effects in multiple mutant hSOD1 models of amyotrophic lateral sclerosis by activating ERK. Neuroscience 379). IBRO. https://doi.org/10.1016/j.neuroscience.2018.03.008
Xing Y, Li N, Zhou D, Chen G, Jiao K, Wang W, Hou Y (2017) Sesquiterpene coumarins from ferula sinkiangensis act as neuroinflammation inhibitors. Planta Med 83(1-02):135–142. https://doi.org/10.1055/s-0042-109271
Yáñez M, Galán L, Matías-Guiu J, Vela A, Guerrero A, García AG (2011) CSF from amyotrophic lateral sclerosis patients produces glutamate independent death of rat motor brain cortical neurons: Protection by resveratrol but not riluzole. Brain Res 1423:77–86. https://doi.org/10.1016/j.brainres.2011.09.025
Yang J, Zhang P, Hu Y, Liu T, Sun J, Wang X (2019) Synthesis and biological evaluation of 3-arylcoumarins as potential anti-Alzheimer's disease agents. J Enzyme Inhib Med Chem 34(1):651–656. https://doi.org/10.1080/14756366.2019.1574297
Zhao L, Zhang J, Liu T, Mou H, Wei C, Hu D, Song B (2020) Design, synthesis, and antiviral activities of coumarin derivatives containing dithioacetal structures. J Agric Food Chem 68(4):975–981. https://doi.org/10.1021/acs.jafc.9b06861
Zhu JJ, Jiang JG (2018) pharmacological and nutritional effects of natural coumarins and their structure-activity relationships. Mol Nutr Food Res e1701073. https://doi.org/10.1002/mnfr.201701073
Zhuang X, Li X, Zhao B, Liu Z, Song F, Lu J (2020) Native mass spectrometry based method for studying the interactions between superoxide dismutase 1 and Stilbenoids. ACS Chem Neurosci 11(2):184–190. https://doi.org/10.1021/acschemneuro.9b00574
Zhou Y, Fang SH, Ye YL, Chu LS, Zhang WP, Wang ML, Wei EQ (2006) Caffeic acid ameliorates early and delayed brain injuries after focal cerebral ischemia in rats. Acta pharmacologica Sinica 27(9):1103–1110. https://doi.org/10.1111/j.1745-7254.2006.00406.x
Zu T, Liu Y, Bañez-Coronel M, Reid T, Pletnikova O, Lewis J, Miller TM, Harms MB, Falchook AE, Subramony SH, Ostrow LW, Rothstein JD, Troncoso JC, Ranum LP (2013) RAN proteins and RNA foci from antisense transcripts in C9ORF72 ALS and frontotemporal dementia. Proceedings of the National Academy of Sciences of the United States of America 110(51):E4968–E4977. https://doi.org/10.1073/pnas.1315438110
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We are grateful to the Multicentric Postgraduate Program in Biochemistry and Molecular Biology and Postgraduate Program in Immunology at the Federal University of Bahia.
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LO, RC, CSS, ET, VDAS, and SLC were supported by grants from the Coordenação de Apoio de Pessoal de Nível Superior (CAPES/EDITAL COOPBRASS Processo Nº 05/2019). SLC was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ—research fellowship).
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de Oliveira, L.M.G., Carreira, R.B., de Oliveira, J.V.R. et al. Impact of Plant-Derived Compounds on Amyotrophic Lateral Sclerosis. Neurotox Res 41, 288–309 (2023). https://doi.org/10.1007/s12640-022-00632-1
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DOI: https://doi.org/10.1007/s12640-022-00632-1