Abstract
Parkinson's disease (PD) is a neurodegenerative disease associated with motor deficiency and rigidity. The genetic risks of the disease is reported to be between 5 and 10% depending on the background of the population. While PD is not considered an immune-mediated disease, amounting evidence in recent years suggests a major role of inflammation in the progression of PD. Markers of inflammation can be found around the regions of risk and adjacent to the appearance of Lewy bodies within the basal ganglia and the substantia nigra (SN) that are associated with PD pathology. Microglia, an important type of brain cell, has been reported to play a major role in mediating neuroinflammation and in PD disease pathology. This review aims to point out the potential role of microglia in disease progression and suggest that the interaction of microglia with the dopaminergic neurons may also facilitate the specificity of the disease in brain regions affected by PD.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Alvarez-Erviti L, Couch Y, Richardson J, Cooper JM, Wood MJA (2011) Alpha-synuclein release by neurons activates the inflammatory response in a microglial cell line. Neurosci Res 69(4):337–342. https://doi.org/10.1016/j.neures.2010.12.020
Aratani Y (2018) Myeloperoxidase: its role for host defense, inflammation, and neutrophil function. Arch Biochem Biophys 640:47–52. https://doi.org/10.1016/j.abb.2018.01.004
Bachiller S, Jiménez-Ferrer I, Paulus A, Yang Y, Swanberg M, Deierborg T, Boza-Serrano A (2018) Microglia in neurological diseases: a road map to brain-disease dependent-inflammatory response. Front Cell Neurosci 12:1–17. https://doi.org/10.3389/fncel.2018.00488
Blauwendraat C, Nalls MA, Singleton AB (2020) The genetic architecture of Parkinson’s disease. Lancet Neurol 19(2):170–178. https://doi.org/10.1016/S1474-4422(19)30287-X
Block ML, Zecca L, Hong JS (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 8(1):57–69. https://doi.org/10.1038/nrn2038
Boche D, Perry VH, Nicoll JAR (2013) Review: activation patterns of microglia and their identification in the human brain. Neuropathol Appl Neurobiol 39(1):3–18. https://doi.org/10.1111/nan.12011
Boeve BF (2007) Parkinson-related dementias. Neurol Clin 25(3):761–781. https://doi.org/10.1016/j.ncl.2007.04.002
Braak H, Tredici KD, Rüb U, de Vos RA, Jansen Steur ENH, Braak E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging 24(2):197–211. https://doi.org/10.1016/S0197-4580(02)00065-9
Cantarella G, Di Benedetto G, Puzzo D, Privitera L, Loreto C, Saccone S, Giunta S, Palmeri A, Bernardini R (2015) Neutralization of TNFSF10 ameliorates functional outcome in a murine model of Alzheimer’s disease. Brain 138(1):203–216. https://doi.org/10.1093/brain/awu318
Center for Devices and Radiological Health (2017) Premarket approval (PMA) database. US Food and Drug Administration, Washington
Chang JY, Liu LZ (2000) Catecholamines inhibit microglial nitric oxide production. Brain Res Bull 52(6):525–530. https://doi.org/10.1016/S0361-9230(00)00291-4
Clark AK, Gruber-Schoffnegger D, Drdla-Schutting R, Gerhold KJ, Malcangio M, Sandkuhler J (2015) Selective activation of microglia facilitates synaptic strength. J Neurosci 35(11):4552–4570. https://doi.org/10.1523/JNEUROSCI.2061-14.2015
Codolo G, Plotegher N, Pozzobon T, Brucale M, Tessari I, Bubacco L, de Bernard M (2013) Triggering of inflammasome by aggregated α-synuclein, an inflammatory response in synucleinopathies. PLoS ONE 8(1):e55375. https://doi.org/10.1371/journal.pone.0055375
De Jong EK, De Haas AH, Brouwer N, Van Weering HRJ, Hensens M, Bechmann I, Pratley P, Wesseling E, Boddeke HWGM, Biber K (2008) Expression of CXCL4 in microglia in vitro and in vivo and its possible signaling through CXCR3. J Neurochem 105(5):1726–1736. https://doi.org/10.1111/j.1471-4159.2008.05267.x
Dickson DW (2012) Parkinson’s disease and Parkinsonism: neuropathology. Cold Spring Harbor Perspect Med 2(8):a009258–a009258. https://doi.org/10.1101/cshperspect.a009258
Dong J, Li S, Mo J-L, Cai H-B, Le W-D (2016) Nurr1-based therapies for Parkinson’s disease. CNS Neurosci Ther 22(5):351–359. https://doi.org/10.1111/cns.12536
Doorn KJ, Moors T, Drukarch B, van de Berg WDJ, Lucassen PJ, van Dam AM (2014) Microglial phenotypes and toll-like receptor 2 in the substantia nigra and hippocampus of incidental Lewy body disease cases and Parkinson’s disease patients. Acta Neuropathol Commun 2(1):1–17. https://doi.org/10.1186/s40478-014-0090-1
Dos-Santos-Pereira M, Acuña L, Hamadat S, Rocca J, González-Lizárraga F, Chehín R, Sepulveda-Diaz J, Del-Bel E, Raisman-Vozari R, Michel PP (2018) Microglial glutamate release evoked by α-synuclein aggregates is prevented by dopamine. Glia 66(11):2353–2365. https://doi.org/10.1002/glia.23472
Ferreira SA, Romero-Ramos M (2018) Microglia response during Parkinson’s disease: alpha-synuclein intervention. Front Cell Neurosci. https://doi.org/10.3389/fncel.2018.00247
Foltynie T (2015) Can Parkinson’s disease be cured by stimulating neurogenesis? J Clin Investig 125(3):978–980. https://doi.org/10.1172/JCI80822
Frenkel D (2015) A new TRAIL in Alzheimer’s disease therapy. Brain. https://doi.org/10.1093/brain/awu334
Fusco G, Chen SW, Williamson PTF, Cascella R, Perni M, Jarvis JA, Cecchi C, Vendruscolo M, Chiti F, Cremades N, Ying L, Dobson CM, De Simone A (2017) Structural basis of membrane disruption and cellular toxicity by α-synuclein oligomers. Science 358(6369):1440–1443. https://doi.org/10.1126/science.aan6160
Gagne JJ, Power MC (2010) Anti-inflammatory drugs and risk of Parkinson disease: a meta-analysis. Neurology 74(12):995–1002. https://doi.org/10.1212/WNL.0b013e3181d5a4a3
Gellhaar S, Sunnemark D, Eriksson H, Olson L, Galter D (2017) Myeloperoxidase-immunoreactive cells are significantly increased in brain areas affected by neurodegeneration in Parkinson’s and Alzheimer’s disease. Cell Tissue Res 369(3):445–454. https://doi.org/10.1007/s00441-017-2626-8
George S, Rey NL, Tyson T, Esquibel C, Meyerdirk L, Schulz E, Pierce S, Burmeister AR, Madaj Z, Steiner JA, Escobar Galvis ML, Brundin L, Brundin P (2019) Microglia affect α-synuclein cell-to-cell transfer in a mouse model of Parkinson’s disease. Mol Neurodegener 14(1):1–22. https://doi.org/10.1186/s13024-019-0335-3
Gerhard A, Pavese N, Hotton G, Turkheimer F, Es M, Hammers A, Eggert K, Oertel W, Banati RB, Brooks DJ (2006) In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson’s disease. Neurobiol Dis 21(2):404–412. https://doi.org/10.1016/j.nbd.2005.08.002
Goldberg MS, Pisani A, Haburcak M, Vortherms TA, Kitada T, Costa C, Tong Y, Martella G, Tscherter A, Martins A, Bernardi G, Roth BL, Pothos EN, Calabresi P, Shen J (2005) Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial parkinsonism-linked gene DJ-1. Neuron 45(4):489–496. https://doi.org/10.1016/j.neuron.2005.01.041
Gordon R, Albornoz EA, Christie DC, Langley MR, Kumar V, Mantovani S, Robertson AAB, Butler MS, Rowe DB, O’Neill LA, Kanthasamy AG, Schroder K, Cooper MA, Woodruff TM (2018) Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodegeneration in mice. Sci Transl Med 10(465):eaah4066. https://doi.org/10.1126/scitranslmed.aah4066
Haque ME, Akther M, Jakaria M, Kim I, Azam S, Choi D (2020) Targeting the microglial NLRP3 inflammasome and its role in Parkinson’s disease. Mov Disord 35(1):20–33. https://doi.org/10.1002/mds.27874
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
Hoffmann A, Ettle B, Bruno A, Kulinich A, Hoffmann AC, von Wittgenstein J, Winkler J, Xiang W, Schlachetzki JCM (2016) Alpha-synuclein activates BV2 microglia dependent on its aggregation state. Biochem Biophys Res Commun. https://doi.org/10.1016/j.bbrc.2016.09.109
Hong CT, Chan L, Wu D, Chen WT, Chien LN (2019) Antiparkinsonism anticholinergics increase dementia risk in patients with Parkinson’s disease. Parkinsonism Relat Disord 65:224–229. https://doi.org/10.1016/j.parkreldis.2019.06.022
Hong S, Beja-Glasser VF, Nfonoyim BM, Frouin A, Li S, Ramakrishnan S, Merry KM, Shi Q, Rosenthal A, Barres BA, Lemere CA, Selkoe DJ, Stevens B (2016) Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science 352(6286):712–716. https://doi.org/10.1126/science.aad8373
Huang Y, Zhao Z, Wei X, Zheng Y, Yu J, Zheng J, Wang L (2016) Long-term trihexyphenidyl exposure alters neuroimmune response and inflammation in aging rat: relevance to age and Alzheimer’s disease. J Neuroinflamm 13(1):1–16. https://doi.org/10.1186/s12974-016-0640-5
Imamura K, Hishikawa N, Sawada M, Nagatsu T, Yoshida M, Hashizume Y (2003) Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson’s disease brains. Acta Neuropathol 106(6):518–526. https://doi.org/10.1007/s00401-003-0766-2
Jucaite A, Svenningsson P, Rinne JO, Cselényi Z, Varnäs K, Johnström P, Amini N, Kirjavainen A, Helin S, Minkwitz M, Kugler AR, Posener JA, Budd S, Halldin C, Varrone A, Farde L (2015) Effect of the myeloperoxidase inhibitor AZD3241 on microglia: A PET study in Parkinson’s disease. Brain 138(9):2687–2700. https://doi.org/10.1093/brain/awv184
Kalilani L, Friesen D, Boudiaf N, Asgharnejad M (2019) The characteristics and treatment patterns of patients with Parkinson’s disease in the United States and United Kingdom: a retrospective cohort study. PLoS ONE 14(11):1–10. https://doi.org/10.1371/journal.pone.0225723
Keren-Shaul H, Spinrad A, Weiner A, Matcovitch-Natan O, Dvir-Szternfeld R, Ulland TK, David E, Baruch K, Lara-Astaiso D, Toth B, Itzkovitz S, Colonna M, Schwartz M, Amit I (2017) A unique microglia type associated with restricting development of Alzheimer’s disease. Cell 169(7):1276–1290.e17. https://doi.org/10.1016/J.CELL.2017.05.018
Kim CH, Han BS, Moon J, Kim DJ, Shin J, Rajan S, Nguyen QT, Sohn M, Kim WG, Han M, Jeong I, Kim KS, Lee EH, Tu Y, Naffin-Olivos JL, Park CH, Ringe D, Yoon HS, Petsko GA, Kim KS (2015) Nuclear receptor Nurr1 agonists enhance its dual functions and improve behavioral deficits in an animal model of Parkinson’s disease. Proc Natl Acad Sci USA 112(28):8756–8761. https://doi.org/10.1073/pnas.1509742112
Koenig J, Dulla C (2018) Complements to the chef: are microglia eating neurons in the epileptic brain? Epilepsy Curr 18(2):128–130. https://doi.org/10.5698/1535-7597.18.2.128
L’Episcopo F, Tirolo C, Testa N, Caniglia S, Morale MC, Impagnatiello F, Marchetti B (2011) Switching the microglial harmful phenotype promotes lifelong restoration of substantia nigra dopaminergic neurons from inflammatory neurodegeneration in aged mice. Rejuvenation Res. https://doi.org/10.1089/rej.2010.1134
Lawson LJ, Perry VH, Dri P, Gordon S (1990) Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience 39(1):151–170. https://doi.org/10.1016/0306-4522(90)90229-W
Lecours C, Bordeleau M, Cantin L, Parent M, di Paolo T, Tremblay MÈ (2018) Microglial implication in Parkinson’s disease: loss of beneficial physiological roles or gain of inflammatory functions? Front Cell Neurosci 12:1–8. https://doi.org/10.3389/fncel.2018.00282
Leplus A, Lauritzen I, Melon C, Kerkerian-Le Goff L, Fontaine D, Checler F (2019) Chronic fornix deep brain stimulation in a transgenic Alzheimer’s rat model reduces amyloid burden, inflammation, and neuronal loss. Brain Struct Funct 224(1):363–372. https://doi.org/10.1007/s00429-018-1779-x
Li Y, Du X, Liu C, Wen Z, Du J (2012) Reciprocal regulation between resting microglial dynamics and neuronal activity in vivo. Dev Cell 23(6):1189–1202. https://doi.org/10.1016/j.devcel.2012.10.027
Liu M, Bing G (2011) Lipopolysaccharide animal models for Parkinson’s disease. Parkinson’s Dis 2011:1–7. https://doi.org/10.4061/2011/327089
Loeffler DA, Camp DM, Conant SB (2006) Complement activation in the Parkinson’s disease substantia nigra: an immunocytochemical study. J Neuroinflamm 3(1):29. https://doi.org/10.1186/1742-2094-3-29
McGeer PL, Itagaki S, Boyes BE, McGeer EG (1988) Reactive microglia are positive for HLA-DR in the: substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology 38(8):1285–1291. https://doi.org/10.1212/wnl.38.8.1285
Meade RM, Fairlie DP, Mason JM (2019) Alpha-synuclein structure and Parkinson’s disease—lessons and emerging principles. Mol Neurodegener 14(1):29. https://doi.org/10.1186/s13024-019-0329-1
Moehle MS, Webber PJ, Tse T, Sukar N, Standaert DG, DeSilva TM, Cowell RM, West AB (2012) LRRK2 inhibition attenuates microglial inflammatory responses. J Neurosci 32(5):1602–1611. https://doi.org/10.1523/JNEUROSCI.5601-11.2012
Mount MP, Lira A, Grimes D, Smith PD, Faucher S, Slack R, Anisman H, Hayley S, Park DS (2007) Involvement of interferon-γ in microglial-mediated loss of dopaminergic neurons. J Neurosci 27(12):3328–3337. https://doi.org/10.1523/JNEUROSCI.5321-06.2007
Mulas G, Espa E, Fenu S, Spiga S, Cossu G, Pillai E, Carboni E, Simbula G, Jadžić D, Angius F, Spolittu S, Batetta B, Lecca D, Giuffrida A, Carta AR (2016) Differential induction of dyskinesia and neuroinflammation by pulsatile versus continuous L-DOPA delivery in the 6-OHDA model of Parkinson’s disease. Exp Neurol 286:83–92. https://doi.org/10.1016/j.expneurol.2016.09.013
Nagatsu T, Sawada M (2005) Inflammatory process in Parkinsons disease: role for cytokines. Curr Pharm Des 11(8):999–1016. https://doi.org/10.2174/1381612053381620
Nakazato T, Sagawa M, Yamato K, Xian M, Yamamoto T, Suematsu M, Ikeda Y, Kizaki M (2007) Myeloperoxidase is a key regulator of oxidative stress-mediated apoptosis in myeloid leukemic cells. Clin Cancer Res 13(18):5436–5445. https://doi.org/10.1158/1078-0432.CCR-07-0481
Nash Y, Schmukler E, Trudler D, Pinkas-Kramarski R, Frenkel D (2017) DJ-1 deficiency impairs autophagy and reduces alpha-synuclein phagocytosis by microglia. J Neurochem. https://doi.org/10.1111/jnc.14222
Nayak D, Roth TL, McGavern DB (2014) Microglia development and function. Annu Rev Immunol 32(1):367–402. https://doi.org/10.1146/annurev-immunol-032713-120240
Ndayisaba A, Jellinger K, Berger T, Wenning GK (2019) TNFα inhibitors as targets for protective therapies in MSA: a viewpoint. J Neuroinflamm 16(1):80. https://doi.org/10.1186/s12974-019-1477-5
Ouchi Y, Yoshikawa E, Sekine Y, Futatsubashi M, Kanno T, Ogusu T, Torizuka T (2005) Microglial activation and dopamine terminal loss in early Parkinson’s disease. Ann Neurol 57(2):168–175. https://doi.org/10.1002/ana.20338
Park J, Min JS, Kim B, Chae UB, Yun JW, Choi MS, Kong IK, Chang KT, Lee DS (2015) Mitochondrial ROS govern the LPS-induced pro-inflammatory response in microglia cells by regulating MAPK and NF-κB pathways. Neurosci Lett 584:191–196. https://doi.org/10.1016/j.neulet.2014.10.016
Parkhurst CN, Yang G, Ninan I, Savas JN, Yates JR, Lafaille JJ, Hempstead BL, Littman DR, Gan WB (2013) Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 155(7):1596–1609. https://doi.org/10.1016/j.cell.2013.11.030
Pavlov VA, Wang H, Czura CJ, Friedman SG, Tracey KJ (2003) The cholinergic anti-inflammatory pathway: a missing link in neuroimmunomodulation. Mol Med 9(5–8):125–134. https://doi.org/10.1007/BF03402177
Peri F, Nüsslein-Volhard C (2008) Live imaging of neuronal degradation by microglia reveals a role for v0-ATPase a1 in phagosomal fusion in vivo. Cell 133(5):916–927. https://doi.org/10.1016/j.cell.2008.04.037
Perry VH (2012) Innate inflammation in Parkinson’s disease. Cold Spring Harbor Perspect Med 2(9):a009373–a009373. https://doi.org/10.1101/cshperspect.a009373
Perry VH, Nicoll JAR, Holmes C (2010) Microglia in neurodegenerative disease. Nat Rev Neurol 6(4):193–201. https://doi.org/10.1038/nrneurol.2010.17
Pocock JM, Kettenmann H (2007) Neurotransmitter receptors on microglia. Trends Neurosci 30(10):527–535. https://doi.org/10.1016/j.tins.2007.07.007
Posener JA, Hauser RA, Stieber M, Leventer SM, Eketjäll S, Minkwitz MC, Ingersoll EW, Kugler AR (2014) Safety, tolerability, and pharmacodynamics of AZD3241, a myeloperoxidase inhibitor, in Parkinson’s disease. Mov Disord 29:259–260
Puschmann A (2013) Monogenic Parkinson’s disease and parkinsonism: clinical phenotypes and frequencies of known mutations. Parkinsonism Relat Disord 19(4):407–415. https://doi.org/10.1016/j.parkreldis.2013.01.020
Reynolds AD, Glanzer JG, Kadiu I, Ricardo-Dukelow M, Chaudhuri A, Ciborowski P, Cerny R, Gelman B, Thomas MP, Mosley RL, Gendelman HE (2008) Nitrated alpha-synuclein-activated microglial profiling for Parkinson’s disease. J Neurochem 104(6):1504–1525. https://doi.org/10.1111/j.1471-4159.2007.05087.x
Sadeghian M, Mullali G, Pocock JM, Piers T, Roach A, Smith KJ (2016) Neuroprotection by safinamide in the 6-hydroxydopamine model of Parkinson’s disease. Neuropathol Appl Neurobiol 42(5):423–435. https://doi.org/10.1111/nan.12263
Scheiblich H, Bicker G (2017) Regulation of microglial phagocytosis by RhoA/ROCK-inhibiting drugs. Cell Mol Neurobiol 37(3):461–473. https://doi.org/10.1007/s10571-016-0379-7
Schwartz M, Kipnis J, Rivest S, Prat A (2013) How do immune cells support and shape the brain in health, disease, and aging? J Neurosci 33(45):17587–17596. https://doi.org/10.1523/JNEUROSCI.3241-13.2013
Shigemoto-Mogami Y, Hoshikawa K, Goldman JE, Sekino Y, Sato K (2014) Microglia enhance neurogenesis and oligodendrogenesis in the early postnatal subventricular zone. J Neurosci 34(6):2231–2243. https://doi.org/10.1523/JNEUROSCI.1619-13.2014
Singleton AB, Hardy JA, Gasser T (2017) The birth of the modern era of Parkinson’s disease genetics. J Parkinson’s Dis 7(s1):S87–S93. https://doi.org/10.3233/JPD-179009
Smith GA, Rocha EM, Rooney T, Barneoud P, McLean JR, Beagan J, Osborn T, Coimbra M, Luo Y, Hallett PJ, Isacson O (2015) A Nurr1 agonist causes neuroprotection in a Parkinson’s disease lesion model primed with the toll-like receptor 3 dsRNA inflammatory stimulant poly(I:C). PLoS ONE 10(3):1–14. https://doi.org/10.1371/journal.pone.0121072
Stefanova N, Fellner L, Reindl M, Masliah E, Poewe W, Wenning GK (2011) Toll-like receptor 4 promotes α-synuclein clearance and survival of nigral dopaminergic neurons. Am J Pathol 179(2):954–963. https://doi.org/10.1016/j.ajpath.2011.04.013
Tay TL, Savage JC, Hui CW, Bisht K, Tremblay M-È (2017) Microglia across the lifespan: from origin to function in brain development, plasticity and cognition. J Physiol 595(6):1929–1945. https://doi.org/10.1113/JP272134
Tremblay ME, Cookson MR, Civiero L (2019) Glial phagocytic clearance in Parkinson’s disease. Mol Neurodegener 14(1):1–14. https://doi.org/10.1186/s13024-019-0314-8
Trudler D, Levy-Barazany H, Nash Y, Samuel L, Sharon R, Frenkel D (2020) Alpha synuclein deficiency increases CD4 + T-cells pro-inflammatory profile in a Nurr1-dependent manner. J Neurochem 152(1):61–71. https://doi.org/10.1111/jnc.14871
Trudler D, Nash Y, Frenkel D (2015) New insights on Parkinson’s disease genes: the link between mitochondria impairment and neuroinflammation. J Neural Transm 122(10):1409–1419. https://doi.org/10.1007/s00702-015-1399-z
Trudler D, Weinreb O, Mandel SA, Youdim MBH, Frenkel D (2014) DJ-1 deficiency triggers microglia sensitivity to dopamine toward a pro-inflammatory phenotype that is attenuated by rasagiline. J Neurochem 129(3):434–447. https://doi.org/10.1111/jnc.12633
US Food and Drug Administration (2017) Approved drugs database. US Food and Drug Administration, Washington
Vawter MP, Dillon-Carter O, Tourtellotte WW, Carvey P, Freed WJ (1996) TGFβ1 and TGFβ2 concentrations are elevated in Parkinson’s Disease in ventricular cerebrospinal fluid. Exp Neurol 142(2):313–322. https://doi.org/10.1006/exnr.1996.0200
Vedam-Mai V, Baradaran-Shoraka M, Reynolds BA, Okun MS (2016) Tissue response to deep brain stimulation and microlesion: a comparative study. Neuromodulation 19(5):451–458. https://doi.org/10.1111/ner.12406
Wake H, Moorhouse AJ, Jinno S, Kohsaka S, Nabekura J (2009) Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J Neurosci 29(13):3974–3980. https://doi.org/10.1523/JNEUROSCI.4363-08.2009
Wolf SA, Boddeke HWGM, Kettenmann H (2017) Microglia in physiology and disease. Annu Rev Physiol 79(1):619–643. https://doi.org/10.1146/annurev-physiol-022516-034406
Wu DC, Jackson-Lewis V, Vila M, Tieu K, Teismann P, Vadseth C, Choi DK, Ischiropoulos H, Przedborski S (2002) Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. J Neurosci 22(5):1763–1771. https://doi.org/10.1523/jneurosci.22-05-01763.2002
Xia Y, Zhang G, Han C, Ma K, Guo X, Wan F, Kou L, Yin S, Liu L, Huang J, Xiong N, Wang T (2019) Microglia as modulators of exosomal alpha-synuclein transmission. Cell Death Dis 10(3):174. https://doi.org/10.1038/s41419-019-1404-9
Yoshiyama Y, Kojima A, Itoh K, Uchiyama T, Arai K (2012) Anticholinergics boost the pathological process of neurodegeneration with increased inflammation in a tauopathy mouse model. Neurobiol Dis 45(1):329–336. https://doi.org/10.1016/j.nbd.2011.08.017
Youdim MBH, Bar Am O, Yogev-Falach M, Weinreb O, Maruyama W, Naoi M, Amit T (2005) Rasagiline: neurodegeneration, neuroprotection, and mitochondrial permeability transition. J Neurosci Res 79(1–2):172–179. https://doi.org/10.1002/jnr.20350
Zabel MK, Kirsch WM (2013) From development to dysfunction: microglia and the complement cascade in CNS homeostasis. Ageing Res Rev 12(3):749–756. https://doi.org/10.1016/j.arr.2013.02.001
Zeuner KE, Schäffer E, Hopfner F, Brüggemann N, Berg D (2019) Progress of pharmacological approaches in Parkinson’s disease. Clin Pharmacol Ther 105(5):1106–1120. https://doi.org/10.1002/cpt.1374
Zhang W, Wang T, Pei Z, Miller DS, Wu X, Block ML, Wilson B, Zhang W, Zhou Y, Hong J, Zhang J (2005) Aggregated α-synuclein activates microglia: a process leading to disease progression in Parkinson’s disease. FASEB J 19(6):533–542. https://doi.org/10.1096/fj.04-2751com
Acknowledgements
This study was supported by a grant from Shoham fund for Parkinson's Disease Research (to D.F.)
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Lazdon, E., Stolero, N. & Frenkel, D. Microglia and Parkinson's disease: footprints to pathology. J Neural Transm 127, 149–158 (2020). https://doi.org/10.1007/s00702-020-02154-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00702-020-02154-6