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A critical role for GM1 ganglioside in the pathophysiology and potential treatment of Parkinson’s disease

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Abstract

Parkinson’s disease (PD) is slowly progressing neurodegenerative disorder that affects millions of patients worldwide. While effective symptomatic therapies for PD exist, there is no currently available disease modifying agent to slow or stop the progression of the disease. Many years of research from various laboratories around the world have provided evidence in favor of the potential ability of GM1 ganglioside to be a disease modifying agent for PD. In this paper, information supporting the use of GM1 as a disease modifying therapeutic for PD is reviewed along with information concerning the role that deficiencies in GM1 ganglioside (and potentially other important brain gangliosides) may play in the pathogenesis of PD.

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References

  1. Marras, C., Tanner, C.M.: The epidemiology of Parkinson's disease. In: Watts, R.L., Koller, W.C. (eds.) Movememnt Disorders Neurological Principles and Pratice, pp. 177–196. McGraw-Hill, New York (2002)

    Google Scholar 

  2. Dorsey, E.R., Constantinescu, R., Thompson, J.P., Biglan, K.M., Holloway, R.G., Kieburtz, K., Marshall, F.J., Ravina, B.M., Schifitto, G., Siderowf, A., Tanner, C.M.: Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology. 68(5), 384–386 (2007). https://doi.org/10.1212/01.wnl.0000247740.47667.03

    Article  CAS  PubMed  Google Scholar 

  3. Schneider, J.S., Gollomp, S.M., Sendek, S., Colcher, A., Cambi, F., Du, W.: A randomized, controlled, delayed start trial of GM1 ganglioside in treated Parkinson's disease patients. J. Neurol. Sci. 324(1–2), 140–148 (2013). https://doi.org/10.1016/j.jns.2012.10.024

    Article  CAS  PubMed  Google Scholar 

  4. Agnati, L.F., Fuxe, K., Calza, L., Benfenati, F., Cavicchioli, L., Toffano, G., Goldstein, M.: Gangliosides increase the survival of lesioned nigral dopamine neurons and favour the recovery of dopaminergic synaptic function in striatum of rats by collateral sprouting. Acta Physiol. Scand. 119(4), 347–363 (1983). https://doi.org/10.1111/j.1748-1716.1983.tb07363.x

    Article  CAS  PubMed  Google Scholar 

  5. Toffano, G., Savoini, G., Moroni, F., Lombardi, G., Calza, L., Agnati, L.F.: GM1 ganglioside stimulates the regeneration of dopaminergic neurons in the central nervous system. Brain Res. 261(1), 163–166 (1983)

    Article  CAS  Google Scholar 

  6. Wu, G., Lu, Z.H., Kulkarni, N., Ledeen, R.W.: Deficiency of ganglioside GM1 correlates with Parkinson's disease in mice and humans. J. Neurosci. Res. 90(10), 1997–2008 (2012). https://doi.org/10.1002/jnr.23090

    Article  CAS  PubMed  Google Scholar 

  7. Schneider, J.S., Yuwiler, A.: GM1 ganglioside treatment promotes recovery of striatal dopamine concentrations in the mouse model of MPTP-induced parkinsonism. Exp. Neurol. 105(2), 177–183 (1989)

    Article  CAS  Google Scholar 

  8. Schneider, J.S., Aras, R., Williams, C.K., Koprich, J.B., Brotchie, J.M., Singh, V.: GM1 ganglioside modifies alpha-Synuclein toxicity and is neuroprotective in a rat alpha-Synuclein model of Parkinson's disease. Sci. Rep. 9(1), 8362 (2019). https://doi.org/10.1038/s41598-019-42847-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Schneider, J.S., Pope, A., Simpson, K., Taggart, J., Smith, M.G., DiStefano, L.: Recovery from experimental parkinsonism in primates with GM1 ganglioside treatment. Science. 256(5058), 843–846 (1992)

    Article  CAS  Google Scholar 

  10. Verma, M., Schneider, J.S.: siRNA-mediated knockdown of B3GALT4 decreases GM1 ganglioside expression and enhances vulnerability for neurodegeneration. Mol. Cell. Neurosci. 95, 25–30 (2019). https://doi.org/10.1016/j.mcn.2019.01.001

    Article  CAS  PubMed  Google Scholar 

  11. Wu, G., Lu, Z.H., Kulkarni, N., Amin, R., Ledeen, R.W.: Mice lacking major brain gangliosides develop parkinsonism. Neurochem. Res. 36(9), 1706–1714 (2011). https://doi.org/10.1007/s11064-011-0437-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Tilson, H.A., Harry, G.J., Nanry, K., Hudson, P.M., Hong, J.S.: Ganglioside interactions with the dopaminergic system of rats. J. Neurosci. Res. 19(1), 88–93 (1988). https://doi.org/10.1002/jnr.490190112

    Article  CAS  PubMed  Google Scholar 

  13. Hadjiconstantinou, M., Rossetti, Z.L., Paxton, R.C., Neff, N.H.: Administration of GM1 ganglioside restores the dopamine content in striatum after chronic treatment with MPTP. Neuropharmacology. 25(9), 1075–1077 (1986)

    Article  CAS  Google Scholar 

  14. Herrero, M.T., Perez-Otano, I., Oset, C., Kastner, A., Hirsch, E.C., Agid, Y., Luquin, M.R., Obeso, J.A., Del Rio, J.: GM-1 ganglioside promotes the recovery of surviving midbrain dopaminergic neurons in MPTP-treated monkeys. Neuroscience. 56(4), 965–972 (1993)

    Article  CAS  Google Scholar 

  15. Hadjiconstantinou, M., Neff, N.H.: Treatment with GM1 ganglioside restores striatal dopamine in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mouse. J. Neurochem. 51(4), 1190–1196 (1988)

    Article  CAS  Google Scholar 

  16. Gupta, M., Schwarz, J., Chen, X.L., Roisen, F.J.: Gangliosides prevent MPTP toxicity in mice--an immunocytochemical study. Brain Res. 527(2), 330–334 (1990). https://doi.org/10.1016/0006-8993(90)91154-9

    Article  CAS  PubMed  Google Scholar 

  17. Fazzini, E., Durso, R., Davoudi, H., Szabo, G.K., Albert, M.L.: GM1 gangliosides alter acute MPTP-induced behavioral and neurochemical toxicity in mice. J. Neurol. Sci. 99(1), 59–68 (1990). https://doi.org/10.1016/0022-510x(90)90199-w

    Article  CAS  PubMed  Google Scholar 

  18. Date, I., Felten, S.Y., Felten, D.L.: Exogenous GM1 gangliosides induce partial recovery of the nigrostriatal dopaminergic system in MPTP-treated young mice but not in aging mice. Neurosci. Lett. 106(3), 282–286 (1989). https://doi.org/10.1016/0304-3940(89)90177-8

    Article  CAS  PubMed  Google Scholar 

  19. Allende, M.L., Proia, R.L.: Lubricating cell signaling pathways with gangliosides. Curr. Opin. Struct. Biol. 12(5), 587–592 (2002)

    Article  CAS  Google Scholar 

  20. Hakomori, S., Igarashi, Y.: Gangliosides and glycosphingolipids as modulators of cell growth, adhesion, and transmembrane signaling. Adv. Lipid Res. 25, 147–162 (1993)

    CAS  PubMed  Google Scholar 

  21. Shield, A.J., Murray, T.P., Board, P.G.: Functional characterisation of ganglioside-induced differentiation-associated protein 1 as a glutathione transferase. Biochem. Biophys. Res. Commun. 347(4), 859–866 (2006). https://doi.org/10.1016/j.bbrc.2006.06.189

    Article  CAS  PubMed  Google Scholar 

  22. Wei, J., Fujita, M., Nakai, M., Waragai, M., Sekigawa, A., Sugama, S., Takenouchi, T., Masliah, E., Hashimoto, M.: Protective role of endogenous gangliosides for lysosomal pathology in a cellular model of synucleinopathies. Am. J. Pathol. 174(5), 1891–1909 (2009). https://doi.org/10.2353/ajpath.2009.080680

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Surmeier, D.J., Guzman, J.N., Sanchez-Padilla, J., Schumacker, P.T.: The role of calcium and mitochondrial oxidant stress in the loss of substantia nigra pars compacta dopaminergic neurons in Parkinson's disease. Neuroscience. 198, 221–231 (2011). https://doi.org/10.1016/j.neuroscience.2011.08.045

    Article  CAS  PubMed  Google Scholar 

  24. Carlson, R.O., Masco, D., Brooker, G., Spiegel, S.: Endogenous ganglioside GM1 modulates L-type calcium channel activity in N18 neuroblastoma cells. J. Neurosci. 14(4), 2272–2281 (1994)

    Article  CAS  Google Scholar 

  25. Martinez, Z., Zhu, M., Han, S., Fink, A.L.: GM1 specifically interacts with alpha-synuclein and inhibits fibrillation. Biochemistry. 46(7), 1868–1877 (2007). https://doi.org/10.1021/bi061749a

    Article  CAS  PubMed  Google Scholar 

  26. Fallon, L., Moreau, F., Croft, B.G., Labib, N., Gu, W.J., Fon, E.A.: Parkin and CASK/LIN-2 associate via a PDZ-mediated interaction and are co-localized in lipid rafts and postsynaptic densities in brain. J. Biol. Chem. 277(1), 486–491 (2002). https://doi.org/10.1074/jbc.M109806200

    Article  CAS  PubMed  Google Scholar 

  27. Hatano, T., Kubo, S., Imai, S., Maeda, M., Ishikawa, K., Mizuno, Y., Hattori, N.: Leucine-rich repeat kinase 2 associates with lipid rafts. Hum. Mol. Genet. 16(6), 678–690 (2007). https://doi.org/10.1093/hmg/ddm013

    Article  CAS  PubMed  Google Scholar 

  28. Bartels, T., Kim, N.C., Luth, E.S., Selkoe, D.J.: N-alpha-acetylation of alpha-synuclein increases its helical folding propensity, GM1 binding specificity and resistance to aggregation. PLoS One. 9(7), e103727 (2014). https://doi.org/10.1371/journal.pone.0103727

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Calne, D.B., Langston, J.W.: Aetiology of Parkinson's disease. Lancet. 2(8365–66), 1457–1459 (1983). https://doi.org/10.1016/s0140-6736(83)90802-4

    Article  CAS  PubMed  Google Scholar 

  30. Landrigan, P.J., Sonawane, B., Butler, R.N., Trasande, L., Callan, R., Droller, D.: Early environmental origins of neurodegenerative disease in later life. Environ. Health Perspect. 113(9), 1230–1233 (2005). https://doi.org/10.1289/ehp.7571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Hadaczek, P., Wu, G., Sharma, N., Ciesielska, A., Bankiewicz, K., Davidow, A.L., Lu, Z.H., Forsayeth, J., Ledeen, R.W.: GDNF signaling implemented by GM1 ganglioside; failure in Parkinson's disease and GM1-deficient murine model. Exp. Neurol. 263, 177–189 (2015). https://doi.org/10.1016/j.expneurol.2014.10.010

    Article  CAS  PubMed  Google Scholar 

  32. Schneider, J.S., Seyfried, T.N., Choi, H.S., Kidd, S.K.: Intraventricular Sialidase administration enhances GM1 ganglioside expression and is partially neuroprotective in a mouse model of Parkinson's disease. PLoS One. 10(12), e0143351 (2015). https://doi.org/10.1371/journal.pone.0143351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Huebecker, M., Moloney, E.B., van der Spoel, A.C., Priestman, D.A., Isacson, O., Hallett, P.J., Platt, F.M.: Reduced sphingolipid hydrolase activities, substrate accumulation and ganglioside decline in Parkinson's disease. Mol. Neurodegener. 14(1), 40 (2019). https://doi.org/10.1186/s13024-019-0339-z

    Article  PubMed  PubMed Central  Google Scholar 

  34. Schneider, J.S.: Altered expression of genes involved in ganglioside biosynthesis in substantia nigra neurons in Parkinson's disease. PLoS One. 13(6), e0199189 (2018). https://doi.org/10.1371/journal.pone.0199189

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Svennerholm, L., Bostrom, K., Jungbjer, B., Olsson, L.: Membrane lipids of adult human brain: lipid composition of frontal and temporal lobe in subjects of age 20 to 100 years. J. Neurochem. 63(5), 1802–1811 (1994). https://doi.org/10.1046/j.1471-4159.1994.63051802.x

    Article  CAS  PubMed  Google Scholar 

  36. Kamel, F.: Epidemiology. Paths from pesticides to Parkinson's. Science. 341(6147), 722–723 (2013). https://doi.org/10.1126/science.1243619

    Article  CAS  PubMed  Google Scholar 

  37. van der Mark, M., Brouwer, M., Kromhout, H., Nijssen, P., Huss, A., Vermeulen, R.: Is pesticide use related to Parkinson disease? Some clues to heterogeneity in study results. Environ. Health Perspect. 120(3), 340–347 (2012). https://doi.org/10.1289/ehp.1103881

    Article  CAS  PubMed  Google Scholar 

  38. Slotkin, T.A., Levin, E.D., Seidler, F.J.: Comparative developmental neurotoxicity of organophosphate insecticides: effects on brain development are separable from systemic toxicity. Environ. Health Perspect. 114(5), 746–751 (2006). https://doi.org/10.1289/ehp.8828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Timofeeva, O.A., Roegge, C.S., Seidler, F.J., Slotkin, T.A., Levin, E.D.: Persistent cognitive alterations in rats after early postnatal exposure to low doses of the organophosphate pesticide, diazinon. Neurotoxicol. Teratol. 30(1), 38–45 (2008). https://doi.org/10.1016/j.ntt.2007.10.002

    Article  CAS  PubMed  Google Scholar 

  40. Levin, E.D., Addy, N., Nakajima, A., Christopher, N.C., Seidler, F.J., Slotkin, T.A.: Persistent behavioral consequences of neonatal chlorpyrifos exposure in rats. Brain Res. Dev. Brain Res. 130(1), 83–89 (2001). https://doi.org/10.1016/s0165-3806(01)00215-2

    Article  CAS  PubMed  Google Scholar 

  41. Levin, E.D., Timofeeva, O.A., Yang, L., Petro, A., Ryde, I.T., Wrench, N., Seidler, F.J., Slotkin, T.A.: Early postnatal parathion exposure in rats causes sex-selective cognitive impairment and neurotransmitter defects which emerge in aging. Behav. Brain Res. 208(2), 319–327 (2010). https://doi.org/10.1016/j.bbr.2009.11.007

    Article  CAS  PubMed  Google Scholar 

  42. Slotkin, T.A., Levin, E.D., Seidler, F.J.: Developmental neurotoxicity of parathion: progressive effects on serotonergic systems in adolescence and adulthood. Neurotoxicol. Teratol. 31(1), 11–17 (2009). https://doi.org/10.1016/j.ntt.2008.08.004

    Article  CAS  PubMed  Google Scholar 

  43. Slotkin, T.A., Seidler, F.J.: Prenatal chlorpyrifos exposure elicits presynaptic serotonergic and dopaminergic hyperactivity at adolescence: critical periods for regional and sex-selective effects. Reprod. Toxicol. 23(3), 421–427 (2007). https://doi.org/10.1016/j.reprotox.2006.07.010

    Article  CAS  PubMed  Google Scholar 

  44. Sledge, D., Yen, J., Morton, T., Dishaw, L., Petro, A., Donerly, S., Linney, E., Levin, E.D.: Critical duration of exposure for developmental chlorpyrifos-induced neurobehavioral toxicity. Neurotoxicol. Teratol. 33(6), 742–751 (2011). https://doi.org/10.1016/j.ntt.2011.06.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Morrison, T., Anderson, D.W., Cai, J., Iacovitti, L., and Schneider, J.S.: Environmental toxicant-induced decrease in GM1 ganglioside expression in dopamine neurons: Potential mechanism contributing to development of Parkinson's disease. Paper presented at the 2014 Neuroscience Meeting Washington, D.C.,

  46. Goldberg, M.S., Lansbury, P.T.: Is there a cause-and-effect relationship between a-synuclein fibrillization and Parkinson's disease? Nat. Cell Biol. 2, 115–119 (2000)

    Article  Google Scholar 

  47. Fujiwara, H., Hasegawa, M., Dohmae, N., Kawashima, A., Masliah, E., Goldberg, M.S., Shen, J., Takio, K., Iwatsubo, T.: alpha-Synuclein is phosphorylated in synucleinopathy lesions. Nat. Cell Biol. 4(2), 160–164 (2002). https://doi.org/10.1038/ncb748

    Article  CAS  PubMed  Google Scholar 

  48. Anderson, J.P., Walker, D.E., Goldstein, J.M., de Laat, R., Banducci, K., Caccavello, R.J., Barbour, R., Huang, J., Kling, K., Lee, M., Diep, L., Keim, P.S., Shen, X., Chataway, T., Schlossmacher, M.G., Seubert, P., Schenk, D., Sinha, S., Gai, W.P., Chilcote, T.J.: Phosphorylation of Ser-129 is the dominant pathological modification of alpha-synuclein in familial and sporadic Lewy body disease. J. Biol. Chem. 281(40), 29739–29752 (2006). https://doi.org/10.1074/jbc.M600933200

    Article  CAS  PubMed  Google Scholar 

  49. Li, J., Uversky, V.N., Fink, A.L.: Effect of familial Parkinson's disease point mutations A30P and A53T on the structural properties, aggregation, and fibrillation of human alpha-synuclein. Biochemistry. 40(38), 11604–11613 (2001). https://doi.org/10.1021/bi010616g

    Article  CAS  PubMed  Google Scholar 

  50. Narhi, L., Wood, S.J., Steavenson, S., Jiang, Y., Wu, G.M., Anafi, D., Kaufman, S.A., Martin, F., Sitney, K., Denis, P., Louis, J.C., Wypych, J., Biere, A.L., Citron, M.: Both familial Parkinson's disease mutations accelerate alpha-synuclein aggregation. J. Biol. Chem. 274(14), 9843–9846 (1999). https://doi.org/10.1074/jbc.274.14.9843

    Article  CAS  PubMed  Google Scholar 

  51. Seyfried, T.N., Choi, H., Chevalier, A., Hogan, D., Akgoc, Z., Schneider, J.S.: Sex-related abnormalities in substantia nigra lipids in Parkinson’s disease. ASN Neuro (2018)

  52. Chu, Y., Dodiya, H., Aebischer, P., Olanow, C.W., Kordower, J.H.: Alterations in lysosomal and proteasomal markers in Parkinson's disease: relationship to alpha-synuclein inclusions. Neurobiol. Dis. 35(3), 385–398 (2009). https://doi.org/10.1016/j.nbd.2009.05.023

    Article  CAS  PubMed  Google Scholar 

  53. Dehay, B., Bove, J., Rodriguez-Muela, N., Perier, C., Recasens, A., Boya, P., Vila, M.: Pathogenic lysosomal depletion in Parkinson's disease. J. Neurosci. 30(37), 12535–12544 (2010). https://doi.org/10.1523/JNEUROSCI.1920-10.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Lee, H.J., Khoshaghideh, F., Patel, S., Lee, S.J.: Clearance of alpha-synuclein oligomeric intermediates via the lysosomal degradation pathway. J. Neurosci. 24(8), 1888–1896 (2004). https://doi.org/10.1523/JNEUROSCI.3809-03.2004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Decressac, M., Mattsson, B., Weikop, P., Lundblad, M., Jakobsson, J., Bjorklund, A.: TFEB-mediated autophagy rescues midbrain dopamine neurons from alpha-synuclein toxicity. Proc. Natl. Acad. Sci. U. S. A. 110(19), E1817–E1826 (2013). https://doi.org/10.1073/pnas.1305623110

    Article  PubMed  PubMed Central  Google Scholar 

  56. Kannarkat, G.T., Boss, J.M., Tansey, M.G.: The role of innate and adaptive immunity in Parkinson's disease. J. Parkinsons Dis. 3(4), 493–514 (2013). https://doi.org/10.3233/JPD-130250

    Article  PubMed  PubMed Central  Google Scholar 

  57. Ho, M.S.: Microglia in Parkinson's disease. Adv. Exp. Med. Biol. 1175, 335–353 (2019). https://doi.org/10.1007/978-981-13-9913-8_13

    Article  CAS  PubMed  Google Scholar 

  58. Bartels, A.L., Willemsen, A.T., Doorduin, J., de Vries, E.F., Dierckx, R.A., Leenders, K.L.: [11C]-PK11195 PET: quantification of neuroinflammation and a monitor of anti-inflammatory treatment in Parkinson's disease? Parkinsonism Relat. Disord. 16(1), 57–59 (2010). https://doi.org/10.1016/j.parkreldis.2009.05.005

    Article  CAS  PubMed  Google Scholar 

  59. Czlonkowska, A., Kohutnicka, M., Kurkowska-Jastrzebska, I., Czlonkowski, A.: Microglial reaction in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induced Parkinson's disease mice model. Neurodegeneration. 5(2), 137–143 (1996). https://doi.org/10.1006/neur.1996.0020

    Article  CAS  PubMed  Google Scholar 

  60. Hoenen, C., Gustin, A., Birck, C., Kirchmeyer, M., Beaume, N., Felten, P., Grandbarbe, L., Heuschling, P., Heurtaux, T.: Alpha-Synuclein proteins promote pro-inflammatory cascades in microglia: stronger effects of the A53T mutant. PLoS One. 11(9), e0162717 (2016). https://doi.org/10.1371/journal.pone.0162717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Joers, V., Tansey, M.G., Mulas, G., Carta, A.R.: Microglial phenotypes in Parkinson's disease and animal models of the disease. Prog. Neurobiol. 155, 57–75 (2017). https://doi.org/10.1016/j.pneurobio.2016.04.006

    Article  CAS  PubMed  Google Scholar 

  62. McGeer, P.L., McGeer, E.G., Kawamata, T., Yamada, T., Akiyama, H.: Reactions of the immune system in chronic degenerative neurological diseases. Can. J. Neurol. Sci. 18(3 Suppl), 376–379 (1991). https://doi.org/10.1017/s0317167100032479

    Article  CAS  PubMed  Google Scholar 

  63. Sanchez-Guajardo, V., Febbraro, F., Kirik, D., Romero-Ramos, M.: Microglia acquire distinct activation profiles depending on the degree of alpha-synuclein neuropathology in a rAAV based model of Parkinson's disease. PLoS One. 5(1), e8784 (2010). https://doi.org/10.1371/journal.pone.0008784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. V. Singh, R.A., G. Singh, J. S. Schneider: GM1 ganglioside as a modifier of alpha-Synuclein toxicity in vivo and in cell culture. Paper presented at the Society for Neuroscience Annual Meeting, Chicago, IL,

  65. Davis, E.J., Foster, T.D., Thomas, W.E.: Cellular forms and functions of brain microglia. Brain Res. Bull. 34(1), 73–78 (1994). https://doi.org/10.1016/0361-9230(94)90189-9

    Article  CAS  PubMed  Google Scholar 

  66. Fernandez-Arjona, M.D.M., Grondona, J.M., Granados-Duran, P., Fernandez-Llebrez, P., Lopez-Avalos, M.D.: Microglia morphological categorization in a rat model of Neuroinflammation by hierarchical cluster and principal components analysis. Front. Cell. Neurosci. 11, 235 (2017). https://doi.org/10.3389/fncel.2017.00235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Young, K., Morrison, H.: Quantifying microglia morphology from photomicrographs of immunohistochemistry prepared tissue using image. J. Vis. Exp. (136), (2018). https://doi.org/10.3791/57648

  68. Schneider, J.S., Roeltgen, D.P., Rothblat, D.S., Chapas-Crilly, J., Seraydarian, L., Rao, J.: GM1 ganglioside treatment of Parkinson's disease: an open pilot study of safety and efficacy. Neurology. 45(6), 1149–1154 (1995)

    Article  CAS  Google Scholar 

  69. Schneider, J.S., Roeltgen, D.P., Mancall, E.L., Chapas-Crilly, J., Rothblat, D.S., Tatarian, G.T.: Parkinson's disease: improved function with GM1 ganglioside treatment in a randomized placebo-controlled study. Neurology. 50(6), 1630–1636 (1998)

    Article  CAS  Google Scholar 

  70. Schneider, J.S., Kean, A., DiStefano, L.: GM1 ganglioside rescues substantia nigra pars compacta neurons and increases dopamine synthesis in residual nigrostriatal dopaminergic neurons in MPTP-treated mice. J. Neurosci. Res. 42(1), 117–123 (1995). https://doi.org/10.1002/jnr.490420113

    Article  CAS  PubMed  Google Scholar 

  71. Schneider, J.S., Sendek, S., Daskalakis, C., Cambi, F.: GM1 ganglioside in Parkinson's disease: results of a five year open study. J. Neurol. Sci. 292(1–2), 45–51 (2010). https://doi.org/10.1016/j.jns.2010.02.009

    Article  CAS  PubMed  Google Scholar 

  72. Schneider, J.S., Cambi, F., Gollomp, S.M., Kuwabara, H., Brasic, J.R., Leiby, B., Sendek, S., Wong, D.F.: GM1 ganglioside in Parkinson's disease: pilot study of effects on dopamine transporter binding. J. Neurol. Sci. 356, 118–123 (2015). https://doi.org/10.1016/j.jns.2015.06.028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Breit, S., Reimold, M., Reischl, G., Klockgether, T., Wullner, U.: [(11)C]d-threo-methylphenidate PET in patients with Parkinson's disease and essential tremor. J. Neural Transm. 113(2), 187–193 (2006). https://doi.org/10.1007/s00702-005-0311-7

    Article  CAS  PubMed  Google Scholar 

  74. Ghidoni, R., Fiorilli, A., Trinchera, M., Venerando, B., Chigorno, V., Tettamanti, G.: Uptake, cell penetration and metabolic processing of exogenously administered GM1 ganglioside in rat brain. Neurochem. Int. 15(4), 455–465 (1989). https://doi.org/10.1016/0197-0186(89)90164-2

    Article  CAS  PubMed  Google Scholar 

  75. Revunov, E., Johnstrom, P., Arakawa, R., Malmquist, J., Jucaite, A., Defay, T., Takano, A., Schou, M.: First radiolabeling of a ganglioside with a positron emitting radionuclide: in vivo PET demonstrates low exposure of Radiofluorinated GM1 in non-human primate brain. ACS Chem. Neurosci. 11(9), 1245–1249 (2020). https://doi.org/10.1021/acschemneuro.0c00161

    Article  CAS  PubMed  Google Scholar 

  76. Di Biase, E., Lunghi, G., Maggioni, M., Fazzari, M., Pome, D.Y., Loberto, N., Ciampa, M.G., Fato, P., Mauri, L., Sevin, E., Gosselet, F., Sonnino, S., Chiricozzi, E.: GM1 oligosaccharide crosses the human blood-brain barrier in vitro by a paracellular route. Int. J. Mol. Sci. 21(8), (2020). https://doi.org/10.3390/ijms21082858

  77. Chiricozzi, E., Di Biase, E., Lunghi, G., Fazzari, M., Loberto, N., Aureli, M., Mauri, L., Sonnino, S.: Turning the spotlight on the oligosaccharide chain of GM1 ganglioside. Glycoconj. J. 38, 101–117 (2021). https://doi.org/10.1007/s10719-021-09974-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Olanow, C.W., Rascol, O., Hauser, R., Feigin, P.D., Jankovic, J., Lang, A., Langston, W., Melamed, E., Poewe, W., Stocchi, F., Tolosa, E.: A double-blind, delayed-start trial of rasagiline in Parkinson's disease. N. Engl. J. Med. 361(13), 1268–1278 (2009). https://doi.org/10.1056/NEJMoa0809335

    Article  CAS  PubMed  Google Scholar 

  79. Desai, B.S., Monahan, A.J., Carvey, P.M., Hendey, B.: Blood-brain barrier pathology in Alzheimer's and Parkinson's disease: implications for drug therapy. Cell Transplant. 16(3), 285–299 (2007). https://doi.org/10.3727/000000007783464731

    Article  PubMed  Google Scholar 

  80. Gray, M.T., Woulfe, J.M.: Striatal blood-brain barrier permeability in Parkinson's disease. J. Cereb. Blood Flow Metab. 35(5), 747–750 (2015). https://doi.org/10.1038/jcbfm.2015.32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Kortekaas, R., Leenders, K.L., van Oostrom, J.C., Vaalburg, W., Bart, J., Willemsen, A.T., Hendrikse, N.H.: Blood-brain barrier dysfunction in parkinsonian midbrain in vivo. Ann. Neurol. 57(2), 176–179 (2005). https://doi.org/10.1002/ana.20369

    Article  CAS  PubMed  Google Scholar 

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Previous research from the Schneider laboratory referred to in this review was funded by grants from the National Institutes of Health, Fidia Pharmaceutical Corp, the F.M. Kirby Foundation, the Marion and Joseph Wesley Fund, the American Parkinson Disease Association, the National Parkinson Foundation, and Qilu Pharmaceutical Co., Ltd. Original research presented in this paper was funded by a grant from Qilu Pharmaceutical Co., Ltd.

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  1. Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, JAH 521, Philadelphia, PA, 19107, USA

    J. S. Schneider

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Research performed by J.S.S. has been funded by Qilu Pharmaceutical Co., Ltd. and Fidia Pharmaceutical Corp, companies with a commercial interest in GM1 ganglioside. The funders had no role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of any manuscripts that emanated from funded projects.

The author is a named inventor on a patent entitled, “Gene Therapies for Neurodegenerative Disorders Targeting Ganglioside Biosynthetic Pathways”, US Patent 10,874,749, assigned to Thomas Jefferson University.

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This article belongs to the Topical Collection: The Glycobiology of Parkinson’s disease

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Schneider, J.S. A critical role for GM1 ganglioside in the pathophysiology and potential treatment of Parkinson’s disease. Glycoconj J 39, 13–26 (2022). https://doi.org/10.1007/s10719-021-10002-2

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