Skip to main content

Advertisement

Log in

Glycoconjugate journal special issue on: the glycobiology of Parkinson’s disease

  • Comprehensive Review Article
  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder that affects over 10 million aging people worldwide. This condition is characterized by the degeneration of dopaminergic neurons in the pars compacta region of the substantia nigra (SNpc) and by aggregation of proteins, commonly α-synuclein (SNCA). The formation of Lewy bodies that encapsulate aggregated proteins in lipid vesicles is a hallmark of PD. Glycosylation of proteins and neuroinflammation are involved in the pathogenesis. SNCA has many posttranslational modifications and interacts with components of membranes that affect aggregation. The large membrane lipid dolichol accumulates in the brain upon age and has a significant effect on membrane structure. The replacement of dopamine and dopaminergic neurons are at the forefront of therapeutic development. This review examines the role of membrane lipids, glycolipids, glycoproteins and dopamine in the aggregation of SNCA and development of PD. We discuss the SNCA-dopamine-neuromelanin-dolichol axis and the role of membranes in neuronal stem cells that could be a regenerative therapy for PD patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Gai, W.P., Yuan, H.X., Li, X.Q., Power, J.T., Blumbergs, P.C., Jensen, P.H.: In situ and in vitro study of colocalization and segregation of alpha-synuclein, ubiquitin, and lipids in Lewy bodies. Exp Neurol. 166(2), 324–333 (2000)

    Article  CAS  PubMed  Google Scholar 

  2. Stefanis, L.: α-Synuclein in Parkinson's disease. Cold Spring Harb Perspect Med. 2(2), a009399 (2012)

  3. Dehay, B., Bourdenx, M., Gorry, P., Przedborski, S., Vila, M., Hunot, S., et al.: Targeting α-synuclein for treatment of Parkinson’s disease: mechanistic and therapeutic considerations. Lancet Neurol. 14(8), 855–866 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Videira, P.A.Q., Castro-Caldas, M.: Linking Glycation and Glycosylation With Inflammation and Mitochondrial Dysfunction in Parkinson’s Disease. Front Neurosci. 12, 381 (2018). https://doi.org/10.3389/fnins.2018.00381

    Article  PubMed  PubMed Central  Google Scholar 

  5. Li, J., Uversky, V.N., Fink, A.L.: Conformational behavior of human alpha-synuclein is modulated by familial Parkinson’s disease point mutations A30P and A53T. Neurotoxicology 23(4–5), 553–567 (2002)

    Article  CAS  PubMed  Google Scholar 

  6. Ulrih, N.P., Barry, C.H., Fink, A.L.: Impact of Tyr to Ala mutations on alpha-synuclein fibrillation and structural properties. Biochim Biophys Acta. 1782, 581–585 (2008)

    Article  CAS  PubMed  Google Scholar 

  7. Dettmer, U., Newman, A.J., von Saucken, V.E., Bartels, T., Selkoe, D.: J. KTKEGV repeat motifs are key mediators of normal α-synuclein tetramerization: their mutation causes excess monomers and neurotoxicity. Proc Natl Acad Sci USA. 112, 9596–9601 (2015). https://doi.org/10.1073/pnas.1505953112

  8. Nuytemans, K., Theuns, J., Cruts, M.V., Broeckhoven, C.: Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: A mutation update. Hum Mutat. 31, 763–780 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Alcalay, R.N., Levy, O.A., Waters, C.C., Fahn, S., Ford, B., Kuo, S.H., et al.: Glucocerebrosidase activity in Parkinson’s disease with and without GBA mutations. Brain 138(Pt 9), 2648–2658 (2015). https://doi.org/10.1093/brain/awv179

    Article  PubMed  PubMed Central  Google Scholar 

  10. Do, J., McKinney, C., Sharma, P., Sidransky, E.: Glucocerebrosidase and its relevance to Parkinson disease. Mol Neurodegener. 14(1), 36 (2019)

    Article  PubMed  PubMed Central  Google Scholar 

  11. Yap, T.L., Gruschus, J.M., Velayati, A., Westbroek, W., Goldin, E., Moaven, N., et al.: Alpha-synuclein interacts with Glucocerebrosidase providing a molecular link between Parkinson and Gaucher diseases. J Biol Chem. 286(32), 28080–28088 (2011). https://doi.org/10.1074/jbc.M111.237859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. López, G.H., Ilincheta de Boschero, M.G., Castagnet, P.I., Giusto, N.M.: Age-associated changes in the content and fatty acid composition of brain glycerophospholipids. Comp Biochem Physiol Part B Biochem. 112, 331–343 (1995). https://doi.org/10.1016/0305-0491(95)00079-8

  13. Ledesma, M.D., Martin, M.G., Dotti, C.G.: Lipid changes in the aged brain: effect on synaptic function and neuronal survival. Prog Lipid Res. 51, 23–35 (2012). https://doi.org/10.1016/j.plipres.2011.11.004

    Article  CAS  PubMed  Google Scholar 

  14. Andersson, M., Appelkvist, E.L., Kristensson, K., Dallner, G.: Distribution of Dolichol and Dolichyl Phosphate in Human Brain. J Neurochem. 49, 685–691 (1987)

    Article  CAS  PubMed  Google Scholar 

  15. Lai, C.S., Schutzbach, J.S.: Localization of Dolichols in Phospholipid Membranes. An ESR Spin Label Study. FEBS Lett 203, 153–156 (1986)

  16. Schutzbach, J.S., Jensen, J.W., Lai, C.S., Monti, J.A.: Membrane Structure and Mannosyltransferase Activities: The Effect of Dolichols on Membranes. Chem. Scr. 27, 109–118 (1987)

    CAS  Google Scholar 

  17. Ward, W.C., Guan, Z., Zucca, F.A., et al.: Identification and quantification of dolichol and dolichoic acid in neuromelanin from substantia nigra of the human brain. J Lipid Res. 48(7), 1457–1462 (2007)

    Article  CAS  PubMed  Google Scholar 

  18. Engelen, M., Vanna, R., Bellei, C., et al.: Neuromelanins of human brain have soluble and insoluble components with dolichols attached to the melanic structure. PLoS One. 7(11), e48490 (2012)

  19. Ono, K.: The Oligomer Hypothesis in α-Synucleinopathy. Neurochem Res. 42(12), 3362–3371 (2017)

    Article  CAS  PubMed  Google Scholar 

  20. Ugalde, C.L., Lawson, V.A., Finkelstein, D.I., Hill, A.F.: The role of lipids in α-synuclein misfolding and neurotoxicity. J Biol Chem. 294(23), 9016–9028 (2019)

    Article  PubMed  PubMed Central  Google Scholar 

  21. Singleton, A.B., Farrer, M., Johnson, J., Singleton, A., Hague, S., Kachergus, J., et al.: α-synuclein locus triplication causes Parkinson’s disease. Science 302, 841 (2003). https://doi.org/10.1126/science.1090278

    Article  CAS  PubMed  Google Scholar 

  22. Oliveira, L.M., Falomir-Lockhart, L.J., Botelho, M.G., Lin, K.H., Wales, P., Koch, J.C., et al.: Elevated α-synuclein caused by SNCA gene triplication impairs neuronal differentiation and maturation in Parkinson’s patient-derived induced pluripotent stem cells. Cell Death Dis. 6(11), e1994 (2015). https://doi.org/10.1038/cddis.2015.318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Sandal, M., Valle, F., Tessari, I., Mammi, S., Bergantino, E., Musiani, F., et al.: Conformational equilibria in monomeric alpha-synuclein at the single-molecule level. PLoS Biol. 6(1), e6 (2008). https://doi.org/10.1371/journal.pbio.0060006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Galvagnion, C., Topgaard, D., Makasewicz, K., Buell, A.K., Linse, S., Sparr, E., Dobson, C.M.: Lipid Dynamics and Phase Transition within α-Synuclein Amyloid Fibrils. J Phys Chem Lett. 10(24), 7872–7877 (2019). https://doi.org/10.1021/acs.jpclett.9b03005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. α-Synuclein membrane interactions and lipid specificity: Jo, E., McLaurin, J. A., Yip, C. M., St. George-Hyslop, P. Fraser, P. E. J Biol Chem. 275, 34328–34334 (2000)

    Google Scholar 

  26. Lee, H.J., Choi, C., Lee, S.J.: Membrane-bound alpha-synuclein has a high aggregation propensity and The ability to seed the aggregation of the cytosolic form. J Biol Chem. 277(1), 671–678 (2002)

    Article  CAS  PubMed  Google Scholar 

  27. 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)

    Article  CAS  PubMed  Google Scholar 

  28. Kubo, S.I.: Membrane lipids as therapeutic targets for Parkinson’s disease: a possible link between Lewy pathology and membrane lipids. Expert Opin Ther Targets. 20(11), 1301–1310 (2016)

    Article  CAS  PubMed  Google Scholar 

  29. Galvagnion, C.: The Role of Lipids Interacting with α-Synuclein in the Pathogenesis of Parkinson’s Disease. J Parkinsons Dis. 7(3), 433–450 (2017)

    Article  CAS  PubMed  Google Scholar 

  30. Hartl, F.U.: Protein Misfolding Diseases. Annu Rev Biochem. 86, 21–26 (2017). https://doi.org/10.1146/annurev-biochem-061516-044518

    Article  CAS  PubMed  Google Scholar 

  31. Brummel, B.E., Braun, A.R., Sachs, J.N.: Polyunsaturated chains in asymmetric lipids disorder raft mixtures and preferentially associate with α-Synuclein. Biochim Biophys Acta Biomembr. 1859(4), 529–536 (2017)

    Article  CAS  PubMed  Google Scholar 

  32. Banks, W.A.: Characteristics of compounds that cross the blood-brain barrier. BMC Neurol. 9 Suppl 1(Suppl 1), S3 (2009). https://doi.org/10.1186/1471-2377-9-S1-S3

  33. Parmar, M.: Towards stem cell based therapies for Parkinson's disease. Development. 145(1), dev156117 (2018).

  34. Reddy, A.P., Ravichandran, J., Carkaci-Salli, N.: Neural regeneration therapies for Alzheimer’s and Parkinson’s disease-related disorders. Biochim Biophys Acta Mol Basis Dis. 1866(4), 165506 (2020). https://doi.org/10.1016/j.bbadis.2019.06.020

    Article  CAS  PubMed  Google Scholar 

  35. Falkenburger, B.H., Saridaki, T., Dinter, E.: Cellular models for Parkinson's disease. J Neurochem. 139 Suppl 1, 121–130 (2016) https://doi.org/10.1111/jnc.13618

  36. Lotharius, J., Falsig, J., van Beek, J., Payne, S., Dringen, R., Brundin, P., Leist, M.: Progressive degeneration of human mesencephalic neuron-derived cells triggered by dopamine-dependent oxidative stress is dependent on the mixed-lineage kinase pathway. J Neurosci. 25(27), 6329–6342 (2005). https://doi.org/10.1523/JNEUROSCI.1746-05.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Wu, G., Lu, Z.H., Seo, J.H., Alselehdar, S.K., DeFrees, S., Ledeen, R.W.: Mice deficient in GM1 manifest both motor and non-motor symptoms of Parkinson’s disease; successful treatment with synthetic GM1 ganglioside. Exp Neurol. 329, 113284 (2020). https://doi.org/10.1016/j.expneurol.2020.113284

    Article  CAS  PubMed  Google Scholar 

  38. Mesa-Herrera, F., Taoro-González, L., Valdés-Baizabal, C., Diaz, M., Marín, R.: Lipid and Lipid Raft Alteration in Aging and Neurodegenerative Diseases: A Window for the Development of New Biomarkers. Int J Mol Sci. 20(15), 3810 (2019). https://doi.org/10.3390/ijms20153810

    Article  CAS  PubMed Central  Google Scholar 

  39. Fabelo, N., Martín, V., Santpere, G., Marín, R., Torrent, L., Ferrer, I., Díaz, M.: Severe alterations in lipid composition of frontal cortex lipid rafts from Parkinson’s disease and incidental Parkinson’s disease. Mol Med. 17(9–10), 1107–1118 (2011). https://doi.org/10.2119/molmed.2011.00119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Powers, R., Lei, S., Anandhan, A., Marshall, D.D., Worley, B., Cerny, R.L., et al.: Metabolic Investigations of the Molecular Mechanisms Associated with Parkinson’s Disease. Metabolites 7(2), 22 (2017). https://doi.org/10.3390/metabo7020022

    Article  CAS  PubMed Central  Google Scholar 

  41. Viana, S.D., Valero, J., Rodrigues-Santos, P., Couceiro, P., Silva, A.M., Carvalho, F., et al.: Regulation of striatal astrocytic receptor for advanced glycation end-products variants in an early stage of experimental Parkinson’s disease. J Neurochem. 138(4), 598–609 (2016). https://doi.org/10.1111/jnc.13682

    Article  CAS  PubMed  Google Scholar 

  42. Padmaraju, V., Bhaskar, J.J., Prasada Rao, U.J., Salimath, P.V., Rao, K.S.: Role of advanced glycation on aggregation and DNA binding properties of alpha-synuclein. J Alzheimers Dis. 24(Suppl 2), 211–221 (2011). https://doi.org/10.3233/JAD-2011-101965

    Article  CAS  PubMed  Google Scholar 

  43. Russell, A.C., Šimurina, M., Garcia, M.T., Novokmet, M., Wang, Y., Rudan, I., et al.: The N-glycosylation of immunoglobulin G as a novel biomarker of Parkinson’s disease. Glycobiology 27(5), 501–510 (2017). https://doi.org/10.1093/glycob/cwx022

    Article  CAS  PubMed  Google Scholar 

  44. Le Grand, J.N., Gonzalez-Cano, L., Pavlou, M.A., Schwamborn, J.C.: Neural stem cells in Parkinson’s disease: a role for neurogenesis defects in onset and progression. Cell Mol Life Sci. 72(4), 773–797 (2015). https://doi.org/10.1007/s00018-014-1774-1

    Article  CAS  PubMed  Google Scholar 

  45. Alza, N.P., Iglesias González, P.A., Conde, M.A., Uranga, R.M., Salvador, G.A.: Lipids at the Crossroad of α-Synuclein Function and Dysfunction: Biological and Pathological Implications. Front Cell Neurosci. 13, 175 (2019). https://doi.org/10.3389/fncel.2019.00175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Giasson, B.I., Duda, J.E., Quinn, S.M., Zhang, B., Trojanowski, J.Q., Lee, V.M.: Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein. Neuron 34(4), 521–533 (2002). https://doi.org/10.1016/s0896-6273(02)00682-7

    Article  CAS  PubMed  Google Scholar 

  47. Jankovic, J., Tan, E.K.: Parkinson’s disease: etiopathogenesis and treatment. J Neurol Neurosurg Psychiatry. 91(8), 795–808 (2020). https://doi.org/10.1136/jnnp-2019-322338

    Article  PubMed  Google Scholar 

  48. Bendor, J., Logan, T., Edward, R.H.: The Function of α-Synuclein. Neuro 79(6), 1044–1066 (2013)

    CAS  Google Scholar 

  49. Caputi, V., Giron, M.C.: Microbiome-Gut-Brain Axis and Toll-Like Receptors in Parkinson’s Disease. Int J Mol Sci. 19(6), 1689 (2018). https://doi.org/10.3390/ijms19061689

    Article  CAS  PubMed Central  Google Scholar 

  50. Liddle, R.A.: Parkinson’s disease from the gut. Brain Res. 1693(Pt B), 201–206 (2018). https://doi.org/10.1016/j.brainres.2018.01.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Elfil, M., Kamel, S., Kandil, M., Koo, B.B., Schaefer, S.M.: Implications of the Gut Microbiome in Parkinson's Disease Mov Disord. 35(6), 921–933 (2020). https://doi.org/10.1002/mds.28004

  52. Herath, M., Hosie, S., Bornstein, J.C., Franks, A.E., Hill-Yardin, E.L.: The Role of the Gastrointestinal Mucus System in Intestinal Homeostasis: Implications for Neurological Disorders. Front Cell Infect Microbiol. 10, 248 (2020). https://doi.org/10.3389/fcimb.2020.00248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Fusco, G., Sanz-Hernandez, M., De Simone, A.: Order and disorder in the physiological membrane binding of α-synuclein. Curr Opin Struct Biol. 48, 49–57 (2018). https://doi.org/10.1016/j.sbi.2017.09.004

    Article  CAS  PubMed  Google Scholar 

  54. Badawy, M.M.S., Okada, T., Kajimoto, T., Hirase, M., Matovelo, S., Nakamura, S., et al.: Extracellular α-Synuclein Drives Sphingosine 1-Phosphate Receptor Subtype 1 out of Lipid Rafts, Leading to Impaired Inhibitory G-Protein Signaling. J Biol Chem. 293, 8208–8216 (2018)

    Article  PubMed  PubMed Central  Google Scholar 

  55. Rasheed, M., Liang, J., Wang, C., Deng, Y., Chen, Z.: Epigenetic Regulation of Neuroinflammation in Parkinson’s Disease. Int J Mol Sci. 22(9), 4956 (2021). https://doi.org/10.3390/ijms22094956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. MacMahon Copas, A.N., McComish, S.F., Fletcher, J.M., Caldwell, M.A.: The Pathogenesis of Parkinson’s Disease: A Complex Interplay Between Astrocytes, Microglia, and T Lymphocytes? Front Neurol. 12, 666737 (2021). https://doi.org/10.3389/fneur.2021.666737

    Article  PubMed  PubMed Central  Google Scholar 

  57. Ma, J., Gao, J., Wang, J., Xie, A.: Prion-Like Mechanisms in Parkinson’s Disease. Front Neurosci. 13, 552 (2019). https://doi.org/10.3389/fnins.2019.00552

    Article  PubMed  PubMed Central  Google Scholar 

  58. Cohlberg, J.A., Li, J., Uversky, V.N., Fink, A.L.: Heparin and other glycosaminoglycans stimulate the formation of amyloid fibrils from alpha-synuclein in vitro. Biochemistry 41(5), 1502–1511 (2002). https://doi.org/10.1021/bi011711s

    Article  CAS  PubMed  Google Scholar 

  59. Desplats, P., Lee, H.-J., Bae, E.-J., Patrick, C., Rockenstein, E., Crews, L., et al.: Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein. Proc Natl Acad Sci USA 106, 13010–13015 (2009). https://doi.org/10.1073/pnas.0903691106

    Article  PubMed  PubMed Central  Google Scholar 

  60. Liu, I.H., Uversky, V.N., Munishkina, L.A., Fink, A.L., Halfter, W., Cole, G.J.: Agrin binds alpha-synuclein and modulates alpha-synuclein fibrillation. Glycobiology 15(12), 1320–1331 (2005). https://doi.org/10.1093/glycob/cwj014

    Article  CAS  PubMed  Google Scholar 

  61. Surmeier, D.J.: Determinants of dopaminergic neuron loss in Parkinson’s disease. FEBS J. 285(19), 3657–3668 (2018). https://doi.org/10.1111/febs.14607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Wong, Y.C., Luk, K., Purtell, K., Burke Nanni, S., Stoessl, A.J., Trudeau, L.E., et al.: Neuronal vulnerability in Parkinson disease: Should the focus be on axons and synaptic terminals? Mov Disord. 34(10), 1406–1422 (2019). https://doi.org/10.1002/mds.27823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Karpowicz, R.J., Jr., Trojanowski, J.Q., Lee, V.M.: Transmission of α-synuclein seeds in neurodegenerative disease: recent developments. Lab Invest. 99(7), 971–981 (2019). https://doi.org/10.1038/s41374-019-0195-z

    Article  PubMed  PubMed Central  Google Scholar 

  64. Weber, A.N., Morse, M.A., Gay, N.J.: Four N-linked glycosylation sites in human toll-like receptor 2 cooperate to direct efficient biosynthesis and secretion. J Biol Chem. 279(33), 34589–34594 (2004). https://doi.org/10.1074/jbc.M403830200

    Article  CAS  PubMed  Google Scholar 

  65. Hughes, C.D., Choi, M.L., Ryten, M., Hopkins, L., Drews, A., Botía, J.A., et al.: Picomolar concentrations of oligomeric alpha-synuclein sensitizes TLR4 to play an initiating role in Parkinson’s disease pathogenesis. Acta Neuropathol. 137(1), 103–120 (2019). https://doi.org/10.1007/s00401-018-1907-y

    Article  CAS  PubMed  Google Scholar 

  66. Amith, S.R., Jayanth, P., Franchuk, S., Finlay, T., Seyrantepe, V., Beyaert, R., Pshezhetsky, A.V., Szewczuk, M.R.: Neu1 desialylation of sialyl alpha-2,3-linked beta-galactosyl residues of TOLL-like receptor 4 is essential for receptor activation and cellular signaling. Cell Signal. 22(2), 314–324 (2010). https://doi.org/10.1016/j.cellsig.2009.09.038

    Article  CAS  PubMed  Google Scholar 

  67. Voutilainen, M.H., Arumäe, U., Airavaara, M., Saarma, M.: Therapeutic potential of the endoplasmic reticulum located and secreted CDNF/MANF family of neurotrophic factors in Parkinson's disease. FEBS Lett. 589(24 Pt A), 3739–3748 (2015). https://doi.org/10.1016/j.febslet.2015.09.031

  68. Perez, R.G., Waymire, J.C., Lin, E., Liu, J.J., Guo, F., Zigmond, M.J.: A role for alpha-synuclein in the regulation of dopamine biosynthesis. J Neurosci. 22(8), 3090–3099 (2002). https://doi.org/10.1523/JNEUROSCI.22-08-03090.2002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Venda, L.L., Cragg, S.J., Buchman, V.L., Wade-Martins, R.: α-Synuclein and dopamine at the crossroads of Parkinson’s disease. Trends Neurosci. 33(12), 559–568 (2010). https://doi.org/10.1016/j.tins.2010.09.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Butler, B., Sambo, D., Khoshbouei, H.: Alpha-synuclein modulates dopamine neurotransmission. J Chem Neuroanat. 83–84, 41–49 (2017)

    Article  PubMed  Google Scholar 

  71. Itäaho, K., Court, M.H., Uutela, P., Kostiainen, R., Radominska-Pandya, A., Finel, M.: Dopamine is a low-affinity and high-specificity substrate for the human UDP-glucuronosyltransferase 1A10. Drug Metab Dispos. 37(4), 768–775 (2009). https://doi.org/10.1124/dmd.108.025692

    Article  CAS  PubMed  Google Scholar 

  72. Piras, S., Furfaro, A.L., Domenicotti, C., Traverso, N., Marinari, U.M., Pronzato, M.A., Nitti, M.: RAGE Expression and ROS Generation in Neurons: Differentiation versus Damage. Oxid Med Cell Longev. 2016, 9348651 (2016). https://doi.org/10.1155/2016/9348651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Segura-Aguilar, J., Paris, I., Muñoz, P., Ferrari, E., Zecca, L., Zucca, F.A.: Protective and toxic roles of dopamine in Parkinson’s disease. J Neurochem. 129(6), 898–915 (2014). https://doi.org/10.1111/jnc.12686

    Article  CAS  PubMed  Google Scholar 

  74. Man, W.K., Tahirbegi, B., Vrettas, M.D. et al. The docking of synaptic vesicles on the presynaptic membrane induced by α-synuclein is modulated by lipid composition. Nat Commun 12, 927 (2021). https://doi.org/10.1038/s41467-021-21027-4

  75. Fountaine, T.M., Venda, L.L., Warrick, N., Christian, H.C., Brundin, P., Channon, K.M., Wade-Martins, R.: The effect of alpha-synuclein knockdown on MPP+ toxicity in models of human neurons. Eur J Neurosci. 28(12), 2459–2473 (2008). https://doi.org/10.1111/j.1460-9568.2008.06527.x

    Article  PubMed  PubMed Central  Google Scholar 

  76. Rilstone, J.J., Alkhater, R.A., Minassian, B.A.: Brain dopamine-serotonin vesicular transport disease and its treatment. N Engl J Med. 368(6), 543–550 (2013). https://doi.org/10.1056/NEJMoa1207281

    Article  CAS  PubMed  Google Scholar 

  77. Afonso-Oramas, D., Cruz-Muros, I., Alvarez de la Rosa, D., Abreu, P., Giráldez, T., Castro-Hernández, J., et al.: Dopamine transporter glycosylation correlates with the vulnerability of midbrain dopaminergic cells in Parkinson's disease. Neurobiol Dis. 36(3), 494–508 (2009). https://doi.org/10.1016/j.nbd.2009.09.002

  78. Burré, J., Sharma, M., Tsetsenis, T., Buchman, V., Etherton, M.R., Südhof, T.C.: Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science 329(5999), 1663–1667 (2010). https://doi.org/10.1126/science.1195227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Dearry, A., Gingrich, J.A., Falardeau, P., Fremeau, R.T., Jr., Bates, M.D., Caron, M.G.: Molecular cloning and expression of the gene for a human D1 dopamine receptor. Nature 347(6288), 72–76 (1990). https://doi.org/10.1038/347072a0

    Article  CAS  PubMed  Google Scholar 

  80. Villar, V.A., Jones, J.E., Armando, I., Palmes-Saloma, C., Yu, P., Pascua, A.M., Keever, L., et al.: G protein-coupled receptor kinase 4 (GRK4) regulates the phosphorylation and function of the dopamine D3 receptor. J Biol Chem. 284(32), 21425–21434 (2009). https://doi.org/10.1074/jbc.M109.003665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Albizu, L., Holloway, T., González-Maeso, J., Sealfon, S.C.: Functional crosstalk and heteromerization of serotonin 5-HT2A and dopamine D2 receptors. Neuropharmacology 61(4), 770–777 (2011). https://doi.org/10.1016/j.neuropharm.2011.05.023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Beaulieu, J.M., Gainetdinov, R.R.: The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev. 63(1), 182–217 (2011). https://doi.org/10.1124/pr.110.002642

    Article  CAS  PubMed  Google Scholar 

  83. Li, A., Mishra, Y., Malik, M., Wang, Q., Li, S., Taylor, M., et al.: Evaluation of N-phenyl homopiperazine analogs as potential dopamine D3 receptor selective ligands. Bioorg Med Chem. 21(11), 2988–2998 (2013). https://doi.org/10.1016/j.bmc.2013.03.074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Fishburn, C.S., Elazar, Z., Fuchs, S.: Differential glycosylation and intracellular trafficking for the long and short isoforms of the D2 dopamine receptor. J Biol Chem. 270(50), 29819–29824 (1995). https://doi.org/10.1074/jbc.270.50.29819

    Article  CAS  PubMed  Google Scholar 

  85. Min, C., Zheng, M., Zhang, X., Guo, S., Kwon, K.J., Shin, C.Y., et al.: N-linked Glycosylation on the N-terminus of the dopamine D2 and D3 receptors determines receptor association with specific microdomains in the plasma membrane. Biochim Biophys Acta. 1853(1), 41–51 (2015). https://doi.org/10.1016/j.bbamcr.2014.09.024

    Article  CAS  PubMed  Google Scholar 

  86. Marotta, N.P., Lin, Y.H., Lewis, Y.E., et al.: O-GlcNAc modification blocks the aggregation and toxicity of the protein α-synuclein associated with Parkinson’s disease. Nat Chem. 7(11), 913–920 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Karube, H., Sakamoto, M., Arawaka, S., Hara, S., Sato, H., Ren, C.H., et al.: N-terminal region of α-synuclein is essential for the fatty acid-induced oligomerization of the molecules. FEBS Lett. 582, 3693–3700 (2008). https://doi.org/10.1016/j.febslet.2008.10.001

    Article  CAS  PubMed  Google Scholar 

  88. Giasson, B.I., Murray, I.V., Trojanowski, J.Q., Lee, V.M.: A hydrophobic stretch of 12 amino acid residues in the middle of alpha-synuclein is essential for filament assembly. J Biol Chem. 276(4), 2380–2386 (2001). https://doi.org/10.1074/jbc.M008919200

    Article  CAS  PubMed  Google Scholar 

  89. Afitska, K., Fucikova, A., Shvadchak, V.V., Yushchenko, D.A.: Modification of C Terminus Provides New Insights into the Mechanism of α-Synuclein Aggregation. Biophys J. 113(10), 2182–2191 (2017). https://doi.org/10.1016/j.bpj.2017.08.027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Jo, E., Fuller, N., Rand, R.P., St George-Hyslop, P., Fraser, P.E.: Defective membrane interactions of familial Parkinson’s disease mutant A30P alpha-synuclein. J Mol Biol. 315(4), 799–807 (2002)

    Article  CAS  PubMed  Google Scholar 

  91. Ghosh, D., et al.: alpha-synuclein aggregation and its modulation. Int. J. Biol. Macromol. 100, 37–54 (2017)

    Article  CAS  PubMed  Google Scholar 

  92. Wang, W., Perovic, I., Chittuluru, J., Kaganovich, A., Nguyen, L.T., Liao, J., et al.: A soluble α-synuclein construct forms a dynamic tetramer. Proc Natl Acad Sci U S A. 108(43), 17797–17802 (2011). https://doi.org/10.1073/pnas.1113260108

    Article  PubMed  PubMed Central  Google Scholar 

  93. Trexler, A.J., Rhoades, E.: N-Terminal acetylation is critical for forming a-helical oligomer of a-synuclein. Protein Sci. 21, 601–605 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Zhu, M., Li, J., Fink, A.L.: The association of alpha-synuclein with membranes affects bilayer structure, stability, and fibril formation. J Biol Chem. 278(41), 40186–40197 (2003)

    Article  CAS  PubMed  Google Scholar 

  95. Zhu, M., Fink, A.L.: Lipid binding inhibits alpha-synuclein fibril formation. J Biol Chem. 278(19), 16873–16877 (2003)

    Article  CAS  PubMed  Google Scholar 

  96. Arawaka, S., Sato, H., Sasaki, A., Koyama, S., Kato, T.: Mechanisms underlying extensive Ser129-phosphorylation in α-synuclein aggregates. Acta Neuropathol Commun. 5(1), 48 (2017). https://doi.org/10.1186/s40478-017-0452-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Paleologou, K.E., Oueslati, A., Shakked, G., Rospigliosi, C.C., Kim, H.-Y., Lamberto, G.R., et al.: Phosphorylation at S87 is enhanced in synucleinopathies, inhibits alpha-synuclein oligomerization, and influences synuclein-membrane interactions. J Neurosci. 30, 3184–3198 (2010). https://doi.org/10.1523/JNEUROSCI.5922-09.2010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. O’Leary, E.I., Jiang, Z., Strub, M.P., Lee, J.C.: Effects of phosphatidylcholine membrane fluidity on the conformation and aggregation of N-terminally acetylated α-Synuclein. J Biol Chem. 293, 11195–11205 (2018). https://doi.org/10.1074/jbc.RA118.002780

    Article  PubMed  PubMed Central  Google Scholar 

  99. O’Leary, E.I., Lee, J.C.: Interplay between α-synuclein amyloid formation and membrane structure. Biochim. Biophys. Acta Proteins Proteom. 1867, 483–491 (2018). https://doi.org/10.1016/j.bbapap.2018.09.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. König, A., Vicente Miranda, H., Outeiro, T.F.: Alpha-Synuclein Glycation and the Action of Anti-Diabetic Agents in Parkinson’s Disease. J Parkinsons Dis. 8(1), 33–43 (2018). https://doi.org/10.3233/JPD-171285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Guerrero, E., Vasudevaraju, P., Hegde, M.L., Britton, G.B., Rao, K.S.: Recent advances in α-synuclein functions, advanced glycation, and toxicity: implications for Parkinson’s disease. Mol Neurobiol. 47(2), 525–536 (2013). https://doi.org/10.1007/s12035-012-8328-z

    Article  CAS  PubMed  Google Scholar 

  103. Vicente Miranda, H., Szego, É.M., Oliveira, L.M.A., Breda, C., Darendelioglu, E., de Oliveira, R.M., et al.: Glycation potentiates α-synuclein-associated neurodegeneration in synucleinopathies. Brain. 140(5), 1399–1419 (2017). https://doi.org/10.1093/brain/awx056

  104. Jin, Q., Chen, H., Luo, A., Ding, F., Liu, Z.: S100A14 stimulates cell proliferation and induces cell apoptosis at different concentrations via receptor for advanced glycation end products (RAGE). PLoS ONE 6(4), e19375 (2011). https://doi.org/10.1371/journal.pone.0019375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. De Oliveira, R.M., Vicente Miranda, H., Francelle, L., Pinho, R., Szegö, É.M., Martinho, R., et al.: The mechanism of sirtuin 2-mediated exacerbation of alpha-synuclein toxicity in models of Parkinson disease. PLoS Biol. 15(3), e2000374 (2017). https://doi.org/10.1371/journal.pbio.2000374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. He, Y., Yu, Z., Chen, S.: Alpha-Synuclein Nitration and Its Implications in Parkinson’s Disease. ACS Chem Neurosci. 10(2), 777–782 (2019). https://doi.org/10.1021/acschemneuro.8b00288

    Article  CAS  PubMed  Google Scholar 

  107. Cole, R.N., Hart, G.W.: Cytosolic O-glycosylation is abundant in nerve terminals. J Neurochem. 79(5), 1080–1089 (2001)

    Article  CAS  PubMed  Google Scholar 

  108. Gao, Y., Wells, L., Comer, F.I., Parker, G.J., Hart, G.W.: Dynamic O-glycosylation of nuclear and cytosolic proteins: cloning and characterization of a neutral, cytosolic beta-N-acetylglucosaminidase from human brain. J Biol Chem. 276(13), 9838–9845 (2001). https://doi.org/10.1074/jbc.M010420200

    Article  CAS  PubMed  Google Scholar 

  109. Kang, L., Moriarty, G.M., Woods, L.A., Ashcroft, A.E., Radford, S.E., Baum, J.: N-terminal acetylation of α-synuclein induces increased transient helical propensity and decreased aggregation rates in the intrinsically disordered monomer. Protein Sci. 21(7), 911–917 (2012). https://doi.org/10.1002/pro.2088

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Levine, P.M., et al.: A-Synuclein O-GlcNAcylation alters aggregation and toxicity, revealing certain residues as potential inhibitors of Parkinson’s disease. Proc Natl Acad Sci U S A. 116(5), 1511–1519 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Banerjee, P.S., Lagerlöf, O., Hart, G.W.: Roles of O-GlcNAc in chronic diseases of aging. Mol Aspects Med. 51, 1–15 (2016). https://doi.org/10.1016/j.mam.2016.05.005

    Article  CAS  PubMed  Google Scholar 

  112. Wang, A.C., Jensen, E.H., Rexach, J.E., Vinters, H.V., Hsieh-Wilson, L.C.: Loss of O-GlcNAc glycosylation in forebrain excitatory neurons induces neurodegeneration. Proc Natl Acad Sci U S A. 113, 15120–15125 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Sipione, S., Monyror, J., Galleguillos, D., Steinberg, N., Kadam, V.: Gangliosides in the Brain: Physiology. Pathophysiology and Therapeutic Applications. Front Neurosci. 14, 572965 (2020). https://doi.org/10.3389/fnins.2020.572965

    Article  PubMed  Google Scholar 

  114. 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 10, 1759091418781889 (2018). https://doi.org/10.1177/1759091418781889

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. 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, 40 (2019). https://doi.org/10.1186/s13024-019-0339-z

    Article  PubMed  PubMed Central  Google Scholar 

  116. Lai, C.S., Schutzbach, .JS.: Dolichol Induces Membrane Leakage of Liposomes Composed of Phosphatidylethanolamine and Phosphatidylcholine. FEBS Lett. 169, 279–282 (1984)

  117. Egawa, J., Pearn, M.L., Lemkuil, B.P., Patel, P.M., Head, B.P.: Membrane lipid rafts and neurobiology: age-related changes in membrane lipids and loss of neuronal function. J Physiol. 594(16), 4565–4579 (2016). https://doi.org/10.1113/JP270590

    Article  CAS  PubMed  Google Scholar 

  118. Fecchio, C., Palazzi, L., Polverino de Laureto, P.: α-Synuclein and polyunsaturated fatty acids: molecular basis of the interaction and implication in neurodegeneration. Molecules. 23, E1531 (2018). https://doi.org/10.3390/molecules23071531

  119. Tettamanti, G., Preti, A., Cestaro, B., Venerando, B., Lombardo, A., Ghidoni, R., Sonnino, S.: Gangliosides, neuraminidase and sialyltransferase at the nerve endings. Adv Exp Med Biol. 125, 263–281 (1980). https://doi.org/10.1007/978-1-4684-7844-0_25

    Article  CAS  PubMed  Google Scholar 

  120. Angata, K., Fukuda, M.: Roles of polysialic acid in migration and differentiation of neural stem cells. Methods Enzymol. 479, 25–36 (2010). https://doi.org/10.1016/S0076-6879(10)79002-9

    Article  CAS  PubMed  Google Scholar 

  121. Hildebrandt, H., Dityatev, A.: Polysialic Acid in Brain Development and Synaptic Plasticity. Top Curr Chem. 366, 55–96 (2015). https://doi.org/10.1007/128_2013_446

    Article  CAS  PubMed  Google Scholar 

  122. Schiff, M., Weinhold, B., Grothe, C., Hildebrandt, H.: NCAM and polysialyltransferase profiles match dopaminergic marker gene expression but polysialic acid is dispensable for development of the midbrain dopamine system. J Neurochem. 110(5), 1661–1673 (2009). https://doi.org/10.1111/j.1471-4159.2009.06267.x

    Article  CAS  PubMed  Google Scholar 

  123. Gao, Y., Luan, X., Melamed, J., Brockhausen, I. Role of Glycans on Key Cell Surface Receptors That Regulate Cell Proliferation and Cell Death. Cells. 10(5), 1252 (2021). https://doi.org/10.3390/cells10051252

  124. Woronowicz, A., Amith, S.R., De Vusser, K., Laroy, W., Contreras, R., Basta, S., Szewczuk, M.R.: Dependence of neurotrophic factor activation of Trk tyrosine kinase receptors on cellular sialidase. Glycobiology 17(1), 10–24 (2007). https://doi.org/10.1093/glycob/cwl049

    Article  CAS  PubMed  Google Scholar 

  125. Ledeen, R.W., Wu, G.: Gangliosides, α-Synuclein, and Parkinson’s Disease. Prog Mol Biol Transl Sci. 156, 435–454 (2018). https://doi.org/10.1016/bs.pmbts.2017.12.009

    Article  CAS  PubMed  Google Scholar 

  126. Comoletti, D., Flynn, R., Jennings, L.L., Chubykin, A., Matsumura, T., Hasegawa, H., Südhof, T.C., Taylor, P.: Characterization of the interaction of a recombinant soluble neuroligin-1 with neurexin-1beta. J Biol Chem. 278(50), 50497–50505 (2003). https://doi.org/10.1074/jbc.M306803200

    Article  CAS  PubMed  Google Scholar 

  127. Birol, M., Wojcik, S.P., Miranker, A.D., Rhoades, E.: Identification of N-linked glycans as specific mediators of neuronal uptake of acetylated α-Synuclein. PLoS Bio 17(6), e3000318 (2019). https://doi.org/10.1371/journal.pbio.3000318

    Article  CAS  Google Scholar 

  128. Dikiy, I., Eliezer, D.: Folding and misfolding of alpha-synuclein on membranes. Biochim Biophys Acta. 1818, 1013–1018 (2012). https://doi.org/10.1016/j.bbamem.2011.09.008

    Article  CAS  PubMed  Google Scholar 

  129. Terakawa, M.S., Lee, Y.H., Kinoshita, M., Lin, Y., Sugiki, T., Fukui, N., et al.: Membrane-induced initial structure of α-synuclein control its amyloidogenesis on model membranes. Biochim Biophys Acta. 1860, 757–766 (2018). https://doi.org/10.1016/j.bbamem.2017.12.011

    Article  CAS  Google Scholar 

  130. Lorenzen, N., Lemminger, L., Pedersen, J.N., Nielsen, S.B., Otzen, D.E.: The N-terminus of α-synuclein is essential for both monomeric and oligomeric interactions with membranes. FEBS Lett. 588(3), 497–502 (2014). https://doi.org/10.1016/j.febslet.2013.12.015

    Article  CAS  PubMed  Google Scholar 

  131. Starheim, K.K., Arnesen, T., Gromyko, D., Ryningen, A., Varhaug, J.E., Lillehaug, J.R.: Identification of the human N(alpha)-acetyltransferase complex B (hNatB): a complex important for cell-cycle progression. Biochem J. 415(2), 325–331 (2008). https://doi.org/10.1042/BJ20080658

    Article  CAS  PubMed  Google Scholar 

  132. Fusco, G., Chen, S.W., Williamson, P.T.F., Cascella, R., Perni, M., Jarvis, J.A., et al.: Structural basis of membrane disruption and cellular toxicity by α-synuclein oligomers. Science 358, 1440–1443 (2017). https://doi.org/10.1126/science.aan6160

    Article  CAS  PubMed  Google Scholar 

  133. Shvadchak, V.V., Yushchenko, D.A., Pievo, R., Jovin, T.M.: The mode of α-synuclein binding to membranes depends on lipid composition and lipid to protein ratio. FEBS Lett. 585(22), 3513–3519 (2011). https://doi.org/10.1016/j.febslet.2011.10.006

    Article  CAS  PubMed  Google Scholar 

  134. Mizuno, S., Sasai, H., Kume, A., et al.: Dioleoyl-phosphatidic acid selectively binds to αsynuclein and strongly induces its aggregation. FEBS Lett. 591(5), 784–791 (2017)

    Article  CAS  PubMed  Google Scholar 

  135. Carroll, C.B., Wyse, R.K.H.: Simvastatin as a Potential Disease-Modifying Therapy for Patients with Parkinson’s Disease: Rationale for Clinical Trial, and Current Progress. J Parkinsons Dis. 7(4), 545–568 (2017). https://doi.org/10.3233/JPD-171203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Perrin, R.J., Woods, W.S., Clayton, D.F., George, J.M.: Exposure to long chain polyunsaturated fatty acids triggers rapid multimerization of synucleins. J Biol Chem. 276(45), 41958–41962 (2001)

    Article  CAS  PubMed  Google Scholar 

  137. De Franceschi, G., Frare, E., Pivato, M., Relini, A., Penco, A., Greggio, E., et al.: Structural and morphological characterization of aggregated species of α-synuclein induced by docosahexaenoic acid. J Biol Chem. 286(25), 22262–22274 (2011). https://doi.org/10.1074/jbc.M110.202937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. De Franceschi, G., Fecchio, C., Sharon, R., Schapira, A.H.V., Proukakis, C., Bellotti, V., et al.: α-Synuclein structural features inhibit harmful polyunsaturated fatty acid oxidation, suggesting roles in neuroprotection. J Biol Chem. 292, 6927–6937 (2017). https://doi.org/10.1074/jbc.M116.765149

    Article  PubMed  PubMed Central  Google Scholar 

  139. Davidson, W.S., Jonas, A., Clayton, D.F., George, J.M.: Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes. J Biol Chem. 273(16), 9443–9449 (1998). https://doi.org/10.1074/jbc.273.16.9443

    Article  CAS  PubMed  Google Scholar 

  140. Martinez, Z., Zhu, M., Han, S., Fink, A.L.: GM1 Specifically Interacts with Alpha-Synuclein and Inhibits Fibrillation. Biochem Pharmacol. 46, 1868–1877 (2007)

    CAS  Google Scholar 

  141. 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 

  142. Ledeen, R., Wu, G.: New findings on nuclear gangliosides: overview on metabolism and function. J Neurochem. 116(5), 714–720 (2011). https://doi.org/10.1111/j.1471-4159.2010.07115.x

    Article  CAS  PubMed  Google Scholar 

  143. 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(1), 101–117 (2021). https://doi.org/10.1007/s10719-021-09974-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Galvagnion, C., Buell, A.K., Meisl, G., Michaels, T.C., Vendruscolo, M., Knowles, T.P., Dobson, C.M.: Lipid vesicles trigger α-synuclein aggregation by stimulating primary nucleation. Nat Chem Biol. 11(3), 229–234 (2015). https://doi.org/10.1038/nchembio.1750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Jensen, J.W., Schutzbach, J.S.: Activation of Mannosyltranferase II by Nonbilayer Phospholipids Biochemistry. 23, 1115–1119 (1984)

    CAS  Google Scholar 

  146. Monti, J.A., Christian, S.T., Schutzbach, J.S.: Effects of Dolichol on Membrane Properties. Biochim Biophys Acta. 905, 133–142 (1987)

    Article  CAS  PubMed  Google Scholar 

  147. Adair, W.L. Jr., Keller, R.K.: Dolichol metabolism in rat liver. Determination of the subcellular distribution of dolichyl phosphate and its site and rate of de novo biosynthesis. J Biol Chem. 257(15):8990–8996 (1982)

  148. Rip, J.W., Rupar, C.A., Ravi, K., Carroll, K.K.: Distribution, metabolism and function of dolichol and polyprenols. Prog Lipid Res. 24(4), 269–309 (1985)

    Article  CAS  PubMed  Google Scholar 

  149. Edlund, C., Söderberg, M., Kristensson, K.: Isoprenoids in aging and neurodegeneration. Neurochem Int. 25(1), 35–38 (1994). https://doi.org/10.1016/0197-0186(94)90050-7

    Article  CAS  PubMed  Google Scholar 

  150. Daniels, I., Hemming, F.W.: Changes in murine tissue concentrations of dolichol and dolichol derivatives associated with age. Lipids 25(10), 586–593 (1990). https://doi.org/10.1007/BF02536006

    Article  CAS  PubMed  Google Scholar 

  151. Ward, W.C., Zucca, F.A., Bellei, C., Zecca, L., Simon, J.D.: Neuromelanins in various regions of human brain are associated with native and oxidized isoprenoid lipids. Arch Biochem Biophys. 484(1), 94–99 (2009)

    Article  CAS  PubMed  Google Scholar 

  152. Bergamini, E., Bizzarri, R., Cavallini, G., Cerbai, B., Chiellini, E., Donati, A., et al.: Ageing and oxidative stress: a role for dolichol in the antioxidant machinery of cell membranes? J Alzheimers Di 6(2), 129–135 (2004). https://doi.org/10.3233/jad-2004-6204

    Article  CAS  Google Scholar 

  153. Schutzbach, J.S., Jensen, J.W.: Bilayer Membrane Destabilization Induced by DolichylPhosphate. Chem Phys Lipids. 51, 213–218 (1989)

    Article  CAS  PubMed  Google Scholar 

  154. Buczkowska, A., Swiezewska, E., Lefeber, D.J.: Genetic defects in dolichol metabolism J Inherit Metab Dis. 38, 157–169 (2015)

    Article  CAS  PubMed  Google Scholar 

  155. Bar-On, P., Crews, L., Koob, A.O., Mizuno, H., Adame, A., Spencer, B., et al.: Statins reduce neuronal α-synuclein aggregation in in vitro models of Parkinson’s disease. J Neurochem. 105, 1656–1667 (2008). https://doi.org/10.1111/j.1471-4159.2008.05254.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Atil, B., Berger-Sieczkowski, E., Bardy, J., Werner, M., Hohenegger, M.: In vitro and in vivo downregulation of the ATP binding cassette transporter B1 by the HMG-CoA reductase inhibitor simvastatin. Naunyn Schmiedebergs Arch Pharmacol. 389(1), 17–32 (2016). https://doi.org/10.1007/s00210-015-1169-3

    Article  CAS  PubMed  Google Scholar 

  157. Grabinska, K., A., et al.: cis-Prenyltransferase: New Insights into Protein Glycosylation, Rubber Synthesis, and Human Diseases, J Biol Chem. 219(35), 18582–18590 (2016)

  158. Kharel, Y., Takahashi, S., Yamashita, S., Koyama, T.: In vivo interaction between the human dehydrodolichyl diphosphate synthase and the Niemann-Pick C2 protein revealed by a yeast two-hybrid system. Biochem Biophys Res Commun. 318(1), 198–203 (2004). https://doi.org/10.1016/j.bbrc.2004.04.007

    Article  CAS  PubMed  Google Scholar 

  159. Morava, E., Wevers, R.A., Cantagrel, V., Hoefsloot, L.H., Al-Gazali, L., Schoots, J., et al.: A novel cerebello-ocular syndrome with abnormal glycosylation due to abnormalities in dolichol metabolism. Brain 133(11), 3210–3220 (2010). https://doi.org/10.1093/brain/awq261

    Article  PubMed  PubMed Central  Google Scholar 

  160. Rush, E.T., Baker, C.V., Rizzo, W.B.: Dolichol kinase deficiency (DOLK-CDG): Two new cases and expansion of phenotype. Am J Med Genet A. 173(9), 2428–2434 (2017). https://doi.org/10.1002/ajmg.a.38287

    Article  CAS  PubMed  Google Scholar 

  161. Van Dessel, G., Lagrou, A., Hilderson, H.J., Dierick, W.: Characterization of the in vitro conversion of dolichol to dolichoate in bovine thyroid. Biochim Biophys Acta. 1167(3), 307–315 (1993). https://doi.org/10.1016/0005-2760(93)90234-z

    Article  PubMed  Google Scholar 

  162. Vila, M.: Neuromelanin, aging, and neuronal vulnerability in Parkinson’s disease. Mov. Disord. 34(10), 1440–1451 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Fedorow, H., Pickford, R., Hook, J.M., et al.: Dolichol is the major lipid component of human substantia nigra neuromelanin. J Neurochem. 92(4), 990–995 (2005)

    Article  CAS  PubMed  Google Scholar 

  164. Conway, K.A., Rochet, J.C., Bieganski, R.M., Lansbury, P.T., Jr.: Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct. Science 294(5545), 1346–1349 (2001). https://doi.org/10.1126/science.1063522

    Article  CAS  PubMed  Google Scholar 

  165. Greggio, E., Bergantino, E., Carter, D., Ahmad, R., Costin, G.E., Hearing, V.J., et al.: Tyrosinase exacerbates dopamine toxicity but is not genetically associated with Parkinson’s disease. J Neurochem. 93(1), 246–256 (2005). https://doi.org/10.1111/j.1471-4159.2005.03019.x

    Article  CAS  PubMed  Google Scholar 

  166. Hasegawa, T.: Tyrosinase-expressing neuronal cell line as in vitro model of Parkinson’s disease. Int J Mol Sci. 11(3), 1082–1089 (2010). https://doi.org/10.3390/ijms11031082

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Carballo-Carbajal, I., Laguna, A., Romero-Giménez, J., et al.: Brain tyrosinase overexpression implicates age-dependent neuromelanin production in Parkinson’s disease pathogenesis. Nat Commun. 10, 973 (2019)

    Article  PubMed  PubMed Central  Google Scholar 

  168. Haining, R.L., Achat-Mendes, C.: Neuromelanin, one of the most overlooked molecules in modern medicine, is not a spectator. Neural Regen Res. 12(3), 372–375 (2017). https://doi.org/10.4103/1673-5374.202928

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Zucca, F.A., Vanna, R., Cupaioli, F.A., Bellei, C., De Palma, A., Di Silvestre, D.: Neuromelanin organelles are specialized autolysosomes that accumulate undegraded proteins and lipids in aging human brain and are likely involved in Parkinson’s disease. NPJ Parkinsons Dis. 4, 17 (2018). https://doi.org/10.1038/s41531-018-0050-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. da Silva, F.L., Coelho Cerqueira, E., de Freitas, M.S., Gonçalves, D.L., Costa, L.T., Follmer, C.: Vitamins K interact with N-terminus α-synuclein and modulate the protein fibrillization in vitro. Exploring the interaction between quinones and α-synuclein. Neurochem Int. 62(1), 103–112 (2013). https://doi.org/10.1016/j.neuint.2012.10.001

  171. Oliveri, V.: Toward the discovery and development of effective modulators of α-synuclein amyloid aggregation. Eur J Med Chem. 167, 10–36 (2019). https://doi.org/10.1016/j.ejmech.2019.01.045

    Article  CAS  PubMed  Google Scholar 

  172. Reglodi, D., Renaud, J., Tamas, A., Tizabi, Y., Socías, S.B., Del-Bel, E., Raisman-Vozari, R.: Novel tactics for neuroprotection in Parkinson’s disease: Role of antibiotics, polyphenols and neuropeptides. Prog Neurobiol. 155, 120–148 (2017). https://doi.org/10.1016/j.pneurobio.2015.10.004

    Article  CAS  PubMed  Google Scholar 

  173. Norris, E.H., Giasson, B.I., Hodara, R., Xu, S., Trojanowski, J.Q., Ischiropoulos, H., Lee, V.M.: Reversible inhibition of alpha-synuclein fibrillization by dopaminochrome-mediated conformational alterations. J Biol Chem. 280(22), 21212–21219 (2005). https://doi.org/10.1074/jbc.M412621200

    Article  CAS  PubMed  Google Scholar 

  174. Tagliafierro, L., Chiba-Falek, O.: Up-regulation of SNCA gene expression: implications to synucleinopathies. Neurogenetics 17(3), 145–157 (2016). https://doi.org/10.1007/s10048-016-0478-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Bonuccelli, U., Pavese, N.: Role of dopamine agonists in Parkinson’s disease: an update. Expert Rev Neurother. 7(10), 1391–1399 (2007). https://doi.org/10.1586/14737175.7.10.1391

    Article  CAS  PubMed  Google Scholar 

  176. Liu, Y., Hao, S., Yang, B., Fan, Y., Qin, X., Chen, Y., Hu, J.: Wnt/β-catenin signaling plays an essential role in α7 nicotinic receptor-mediated neuroprotection of dopaminergic neurons in a mouse Parkinson’s disease model. Biochem Pharmacol. 140, 115–123 (2017). https://doi.org/10.1016/j.bcp.2017.05.017

    Article  CAS  PubMed  Google Scholar 

  177. Magistretti, P.J., Geisler, F.H., Schneider, J.S., Li, P.A., Fiumelli, H., Sipione, S.: Gangliosides: Treatment Avenues in Neurodegenerative Disease. Front Neurol. 10, 859 (2019). https://doi.org/10.3389/fneur.2019.00859

    Article  PubMed  PubMed Central  Google Scholar 

  178. Sidorova, Y.A., Volcho, K.P., Salakhutdinov, N.F.: Neuroregeneration in Parkinson’s Disease: From Proteins to Small Molecules. Curr Neuropharmacol. 17(3), 268–287 (2019). https://doi.org/10.2174/1570159X16666180905094123

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Jang, S.E., Qiu, L., Chan, L.L., Tan, E.K., Zeng, L.: Current Status of Stem Cell-Derived Therapies for Parkinson’s Disease: From Cell Assessment and Imaging Modalities to Clinical Trials. Front Neurosci. 14, 558532 (2020). https://doi.org/10.3389/fnins.2020.558532

    Article  PubMed  PubMed Central  Google Scholar 

  180. Chia, Y.C., Anjum, C.E., Yee, H.R., Kenisi, Y., Chan, M.K.S., Wong, M.B.F., Pan, S.Y.: Stem Cell Therapy for Neurodegenerative Diseases: How Do Stem Cells Bypass the Blood-Brain Barrier and Home to the Brain? Stem Cells International. e8889061 (2020)

  181. Goncharova, V., Das, S., Niles, W., Schraufstatter, I., Wong, A.K., Povaly, T., et al.: Homing of neural stem cells from the venous compartment into a brain infarct does not involve conventional interactions with vascular endothelium. Stem Cells Transl Med. 3(2), 229–240 (2014). https://doi.org/10.5966/sctm.2013-0052

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Yagi, H., Kato, K.: Functional roles of glycoconjugates in the maintenance of stemness and differentiation process of neural stem cells. Glycoconj J. 34(6), 757–763 (2017). https://doi.org/10.1007/s10719-016-9707-x

    Article  CAS  PubMed  Google Scholar 

  183. Yu, R.K., Yanagisawa, M.: Glycobiology of neural stem cells. CNS Neurol Disord Drug Targets. 5(4), 415–423 (2006). https://doi.org/10.2174/187152706777950675

    Article  CAS  PubMed  Google Scholar 

  184. Yanagisawa, M., Yu, R.K.: The expression and functions of glycoconjugates in neural stem cells. Glycobiology 17, 57R-74R (2007)

    Article  CAS  PubMed  Google Scholar 

  185. Yuan, S.H., Martin, J., Elia, J., Flippin, J., Paramban, R.I., Hefferan, M.P., et al.: Cell-Surface Marker Signatures for the Isolation of Neural Stem Cells, Glia and Neurons Derived from Human Pluripotent Stem Cells. PLoS One. 6, e17540 (2011)

  186. Yale, A.R., Nourse, J.L., Lee, K.R., Ahmed, S.N., Arulmoli, J., Jiang, A.Y.L., et al.: Cell Surface N-Glycans Influence Electrophysiological Properties and Fate Potential of Neural Stem Cells. Stem Cell Reports. 11, 869–882 (2018)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Murrell, M.P., Yarema, K.J., Levchenko, A.: The systems biology of glycosylation. ChemBioChem 5(10), 1334–1347 (2004). https://doi.org/10.1002/cbic.200400143

    Article  CAS  PubMed  Google Scholar 

  188. Krasnova, L., Wong, C.H.: Exploring human glycosylation for better therapies. Mol Aspects Med. 51, 125–143 (2016). https://doi.org/10.1016/j.mam.2016.05.003

    Article  CAS  PubMed  Google Scholar 

  189. Iqbal, S., Ghanimi Fard, M., Everest-Dass, A., Packer, N.H., Parker, L.M.: Understanding cellular glycan surfaces in the central nervous system. Biochem Soc Trans. 47(1), 89–100 (2019). https://doi.org/10.1042/BST20180330

    Article  CAS  PubMed  Google Scholar 

  190. Cummings, R.D.: Stuck on sugars - how carbohydrates regulate cell adhesion, recognition, and signaling. Glycoconj. J 36(4), 241–257 (2019). https://doi.org/10.1007/s10719-019-09876-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Kirkeby, A., Grealish, S., Wolf, D.A., Nelander, J., Wood, J., Lundblad, M., et al.: Generation of regionally specified neural progenitors and functional neurons from human embryonic stem cells under defined conditions. Cell Rep. 1(6), 703–714 (2012). https://doi.org/10.1016/j.celrep.2012.04.009

    Article  CAS  PubMed  Google Scholar 

  192. Takahashi, J.: Preparing for first human trial of induced pluripotent stem cell-derived cells for Parkinson’s disease: an interview with Jun Takahashi. Regen Med. 14(2), 93–95 (2019). https://doi.org/10.2217/rme-2018-0158

    Article  CAS  PubMed  Google Scholar 

  193. Schweitzer, J.S., Song, B., Herrington, T.M., Park, T.-Y., Lee, N., Ko, S., et al.: Personalized iPSC-Derived Dopamine Progenitor Cells for Parkinson’s Disease. N. Engl. J. Med. 382(20), 1926–1932 (2020). https://doi.org/10.1056/nejmoa1915872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Venkataramana, N.K., Kumar, S.K., Balaraju, S., Radhakrishnan, R.C., Bansal, A., Dixit, A., et al.: Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson’s disease. Transl Res. 155(2), 62–70 (2010). https://doi.org/10.1016/j.trsl.2009.07.006

    Article  CAS  PubMed  Google Scholar 

  195. Lanctot, P.M., Gage, F.H., Varki, A.P.: The Glycans of Stem Cells. Curr Opin Chem Biol. 11, 373–380 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Breimer, M.E., Säljö, K., Barone, A., Teneberg, S.: Glycosphingolipids of human embryonic stem cells. Glycoconj J. 34(6), 713–723 (2017). https://doi.org/10.1007/s10719-016-9706-y

    Article  CAS  PubMed  Google Scholar 

  197. Terashima, M., Amano, M., Onodera, T., Nishimura, S.-I., Iwasaki, N.: Quantitative glycomics monitoring of induced pluripotent- and embryonic stem cells during neuronal differentiation. Stem Cell Research. 13, 454–464 (2014)

    Article  CAS  PubMed  Google Scholar 

  198. Hennen, E., Czopka, T., Faissner, A.: Structurally Distinct LewisX Glycans Distinguish Subpopulations of Neural Stem/Progenitor Cells. J Biol Chem. 286, 16321–16331 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. An, H.J., Gip, P., Kim, .J, Wu, S., Park, K.W., McVaugh, C.T., et al.: Extensive determination of glycan heterogeneity reveals an unusual abundance of high mannose glycans in enriched plasma membranes of human embryonic stem cells. Mol Cell Proteomics. 11(4), M111.010660 (2012). https://doi.org/10.1074/mcp.M111.010660

  200. Yu, R.K., Suzuki, Y., Yanagisawa, M.: Membrane Glycolipids in Stem Cells. FEBS Lett. 584, 1694–1699 (2010)

    Article  CAS  PubMed  Google Scholar 

  201. Li, Y.L., Wu, G.Z., Zeng, L., Dawe, G.S., Sun, L., Loers, G., et al.: Cell surface sialylation and fucosylation are regulated by the cell recognition molecule L1 via PLCgamma and cooperate to modulate embryonic stem cell survival and proliferation. FEBS Lett. 583(4), 703–710 (2009). https://doi.org/10.1016/j.febslet.2009.01.013

    Article  CAS  PubMed  Google Scholar 

  202. Doherty, P., Cohen, J., Walsh, F.S.: Neurite outgrowth in response to transfected N-CAM changes during development and is modulated by polysialic acid. Neuron 5(2), 209–219 (1990). https://doi.org/10.1016/0896-6273(90)90310-c

    Article  CAS  PubMed  Google Scholar 

  203. El Maarouf, A., Yaw, D.M., Rutishauser, U.: Improved stem cell-derived motoneuron survival, migration, sprouting, and innervation with enhanced expression of polysialic acid. Cell Transplant. 24(5), 797–809 (2015). https://doi.org/10.3727/096368914X679228

    Article  PubMed  Google Scholar 

  204. He, H., Nilsson, C.L., Emmett, M.R., Marshall, A.G., Kroes, R.A., Moskal, J.R., et al.: Glycomic and transcriptomic response of GSC11 glioblastoma stem cells to STAT3 phosphorylation inhibition and serum-induced differentiation. J Proteome Res. 9(5), 2098–2108 (2010). https://doi.org/10.1021/pr900793a

    Article  CAS  PubMed  Google Scholar 

  205. Itokazu, Y., Tsai, Y.T., Yu, R.K.: Epigenetic regulation of ganglioside expression in neural stem cells and neuronal cells. Glycoconj J. 34(6), 749–756 (2017). https://doi.org/10.1007/s10719-016-9719-6

    Article  CAS  PubMed  Google Scholar 

  206. Brawner, A.T., Xu, R., Liu, D., Jiang, P.: Generating CNS organoids from human induced pluripotent stem cells for modeling neurological disorders. Int J Physiol Pathophysiol Pharmacol. 9(3), 101–111 (2017)

    CAS  PubMed  PubMed Central  Google Scholar 

  207. Jo, J., Xiao, Y., Sun, A.X., Cukuroglu, E., Tran, H.D., Göke, J., et al.: Midbrain-like Organoids from Human Pluripotent Stem Cells Contain Functional Dopaminergic and Neuromelanin-Producing Neurons. Cell Stem Cell 19(2), 248–257 (2016). https://doi.org/10.1016/j.stem.2016.07.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Kriks, S., Shim, J.W., Piao, J., Ganat, Y.M., Wakeman, D.R., Xie, Z., et al.: Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease. Nature 480(7378), 547–551 (2011). https://doi.org/10.1038/nature10648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Steinbeck, J.A., Studer, L.: Moving stem cells to the clinic: potential and limitations for brain repair. Neuron 86(1), 187–206 (2015). https://doi.org/10.1016/j.neuron.2015.03.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. Tagliafierro, L., Zamora, M.E., Chiba-Falek, O.: Multiplication of the SNCA locus exacerbates neuronal nuclear aging. Hum Mol Genet. 28(3), 407–421 (2019). https://doi.org/10.1093/hmg/ddy355

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The work was supported by the Natural Sciences and Engineering Research Council of Canada.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Inka Brockhausen.

Ethics declarations

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Brockhausen, I., Schutzbach, J., Wang, J. et al. Glycoconjugate journal special issue on: the glycobiology of Parkinson’s disease. Glycoconj J 39, 55–74 (2022). https://doi.org/10.1007/s10719-021-10024-w

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-021-10024-w

Keywords

Navigation