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Simple and Complex Sugars in Parkinson’s Disease: a Bittersweet Taste

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Abstract

Neuronal homeostasis depends on both simple and complex sugars (the glycoconjugates), and derangement of their metabolism is liable to impair neural function and lead to neurodegeneration. Glucose levels boost glycation phenomena, a wide series of non-enzymatic reactions that give rise to various intermediates and end-products that are potentially dangerous in neurons. Glycoconjugates, including glycoproteins, glycolipids, and glycosaminoglycans, contribute to the constitution of the unique features of neuron membranes and extracellular matrix in the nervous system. Glycosylation defects are indeed frequently associated with nervous system disturbances and neurodegeneration. Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms associated with the loss of dopaminergic neurons in the pars compacta of the substantia nigra. Neurons present intracytoplasmic inclusions of α-synuclein aggregates involved in the disease pathogenesis together with the impairment of the autophagy-lysosome function, oxidative stress, and defective traffic and turnover of membrane components. In the present review, we selected relevant recent contributions concerning the direct involvement of glycation and glycosylation in α-synuclein stability, impaired autophagy and lysosomal function in PD, focusing on potential models of PD pathogenesis provided by genetic variants of glycosphingolipid processing enzymes, especially glucocerebrosidase (GBA). Moreover, we collected data aimed at defining the glycomic profile of PD patients as a tool to help in diagnosis and patient subtyping, as well as those pointing to sugar-related compounds with potential therapeutic applications in PD.

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References

  1. Wihan J, Grosch J, Kalinichenko LS, Müller CP, Winkler J, Kohl Z (2019) Layer-specific axonal degeneration of serotonergic fibers in the prefrontal cortex of aged A53T α-synuclein–expressing mice. Neurobiol Aging 80:29–37

    Article  CAS  PubMed  Google Scholar 

  2. Deusser J, Schmidt S, Ettle B, Plötz S, Huber S, Müller CP, Masliah E, Winkler J et al (2015) Serotonergic dysfunction in the A53T alpha-synuclein mouse model of Parkinson’s disease. J Neurochem 135(3):589–597

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kohl Z, Ben Abdallah N, Vogelgsang J, Tischer L, Deusser J, Amato D, Anderson S, Müller CP et al (2016) Severely impaired hippocampal neurogenesis associates with an early serotonergic deficit in a BAC α-synuclein transgenic rat model of Parkinson’s disease. Neurobiol Dis 85:206–217

    Article  CAS  PubMed  Google Scholar 

  4. Nuber S, Rajsombath M, Minakaki G, Winkler J, Müller CP, Ericsson M, Caldarone B, Dettmer U et al (2018) Abrogating native α-Synuclein tetramers in mice causes a L-Dopa-responsive motor syndrome closely resembling Parkinson’s disease. Neuron 100(1):75–90 e5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Balestrino R, Schapira AHV (2020) Parkinson disease. Eur J Neurol 27(1):27–42

    Article  CAS  PubMed  Google Scholar 

  6. Schnaar RL, Gerardy-Schahn R, Hildebrandt H (2014) Sialic acids in the brain: Gangliosides and polysialic acid in nervous system development, stability, disease, and regeneration. Physiol Rev 94(2):461–518

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Heindryckx F, Li JP (2018) Role of proteoglycans in neuro-inflammation and central nervous system fibrosis. Matrix Biol 68–69:589–601

    PubMed  Google Scholar 

  8. Iqbal S, Ghanimi Fard M, Everest-Dass A, Packer NH, Parker LM (2019) Understanding cellular glycan surfaces in the central nervous system. Biochem Soc Trans 47(1):89–100

    Article  CAS  PubMed  Google Scholar 

  9. Lauc G, Vojta A, Zoldos V (2014) Epigenetic regulation of glycosylation is the quantum mechanics of biology. Biochim Biophys Acta 1840(1):65–70

    Article  CAS  PubMed  Google Scholar 

  10. Trinchera M, Zulueta A, Caretti A, Dall'Olio F (2014) Control of glycosylation-related genes by DNA methylation: the intriguing case of the B3GALT5 gene and its distinct promoters. Biology (Basel) 3(3):484–497

    CAS  Google Scholar 

  11. Zulueta A, Caretti A, Signorelli P, Dall'olio F, Trinchera M (2014) Transcriptional control of the B3GALT5 gene by a retroviral promoter and methylation of distant regulatory elements. FASEB J 28(2):946–955

    Article  CAS  PubMed  Google Scholar 

  12. Varki A (2017) Biological roles of glycans. Glycobiology 27(1):3–49

    Article  CAS  PubMed  Google Scholar 

  13. Moll T, Shaw PJ, Cooper-Knock J (2019) Disrupted glycosylation of lipids and proteins is a cause of neurodegeneration. Brain. https://doi.org/10.1093/brain/awz358

  14. Ng BG, Freeze HH (2018) Perspectives on glycosylation and its congenital disorders. Trends Genet 34(6):466–476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Trinchera M, Parini R, Indellicato R, Domenighini R, Dall’Olio F (2018) Diseases of ganglioside biosynthesis: An expanding group of congenital disorders of glycosylation. Mol Genet Metab 124(4):230–237

    Article  CAS  PubMed  Google Scholar 

  16. Schneider JS (1998) GM1 ganglioside in the treatment of Parkinson’s disease. Ann N Y Acad Sci 845:363–373

    Article  CAS  PubMed  Google Scholar 

  17. Ba XH (2016) Therapeutic effects of GM1 on Parkinson’s disease in rats and its mechanism. Int J Neurosci 126(2):163–167

    Article  CAS  PubMed  Google Scholar 

  18. Ryu JK, Shin WH, Kim J, Joe EH, Lee YB, Cho KG, Oh YJ, Kim SU et al (2002) Trisialoganglioside GT1b induces in vivo degeneration of nigral dopaminergic neurons: role of microglia. Glia 38(1):15–23

    Article  PubMed  Google Scholar 

  19. Zappia M, Crescibene L, Bosco D, Arabia G, Nicoletti G, Bagala A, Bastone L, Napoli ID et al (2002) Anti-GM1 ganglioside antibodies in Parkinson’s disease. Acta Neurol Scand 106(1):54–57

    Article  CAS  PubMed  Google Scholar 

  20. Bhuiyan RH, Ohmi Y, Ohkawa Y, Zhang P, Takano M, Hashimoto N, Okajima T, Furukawa K (2019) Loss of enzyme activity in mutated B4GALNT1 gene products in patients with hereditary spastic paraplegia results in relatively mild neurological disorders: Similarity with phenotypes of B4galnt1 knockout mice. Neuroscience 397:94–106

    Article  CAS  PubMed  Google Scholar 

  21. Wu G, Lu ZH, Kulkarni N, Ledeen RW (2012) Deficiency of ganglioside GM1 correlates with Parkinson's disease in mice and humans. J Neurosci Res 90(10):1997–2008

    Article  CAS  PubMed  Google Scholar 

  22. Perissinotto F, Rondelli V, Parisse P, Tormena N, Zunino A, Almasy L, Merkel DG, Bottyan L et al (2019) GM1 Ganglioside role in the interaction of alpha-synuclein with lipid membranes: Morphology and structure. Biophys Chem 255:106272

    Article  CAS  PubMed  Google Scholar 

  23. Schneider JS (2018) Altered expression of genes involved in ganglioside biosynthesis in substantia nigra neurons in Parkinson’s disease. PLoS One 13(6):e0199189

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Seyfried TN, Choi H, Chevalier A, Hogan D, Akgoc Z, Schneider JS (2018) Sex-related abnormalities in substantia nigra lipids in Parkinson’s disease. ASN Neuro 10:1759091418781889

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ma L, Song J, Sun X, Ding W, Fan K, Qi M, Xu Y, Zhang W (2019) Role of microtubule-associated protein 6 glycosylated with gal-(beta-1,3)-GalNAc in Parkinson’s disease. Aging (Albany NY) 11(13):4597–4610

    CAS  Google Scholar 

  26. Hoshi K, Matsumoto Y, Ito H, Saito K, Honda T, Yamaguchi Y, Hashimoto Y (2017) A unique glycan-isoform of transferrin in cerebrospinal fluid: A potential diagnostic marker for neurological diseases. Biochim Biophys Acta Gen Subj 1861(10):2473–2478

    Article  CAS  PubMed  Google Scholar 

  27. Varadi C, Nehez K, Hornyak O, Viskolcz B, Bones J (2019) Serum N-Glycosylation in Parkinson’s disease: a novel approach for potential alterations. Molecules 24(12):E2220

  28. Russell AC, Simurina M, Garcia MT, Novokmet M, Wang Y, Rudan I, Campbell H, Lauc G et al (2017) The N-glycosylation of immunoglobulin G as a novel biomarker of Parkinson’s disease. Glycobiology 27(5):501–510

    Article  CAS  PubMed  Google Scholar 

  29. Birol M, Wojcik SP, Miranker AD, Rhoades E (2019) Identification of N-linked glycans as specific mediators of neuronal uptake of acetylated alpha-synuclein. PLoS Biol 17(6):e3000318

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Kulathingal J, Ko LW, Cusack B, Yen SH (2009) Proteomic profiling of phosphoproteins and glycoproteins responsive to wild-type alpha-synuclein accumulation and aggregation. Biochim Biophys Acta 1794(2):211–224

    Article  CAS  PubMed  Google Scholar 

  31. Afonso-Oramas D, Cruz-Muros I, Alvarez dela Rosa D, Abreu P, Giraldez T, Castro-Hernandez J, Salas-Hernandez J, Lanciego JL et al (2009) Dopamine transporter glycosylation correlates with the vulnerability of midbrain dopaminergic cells in Parkinson's disease. Neurobiol Dis 36(3):494–508

    Article  CAS  PubMed  Google Scholar 

  32. Walimbe T, Panitch A (2019) Proteoglycans in biomedicine: resurgence of an underexploited class of ECM molecules. Front Pharmacol 10:1661

    Article  PubMed  Google Scholar 

  33. Liu IH, Uversky VN, Munishkina LA, Fink AL, Halfter W, Cole GJ (2005) Agrin binds alpha-synuclein and modulates alpha-synuclein fibrillation. Glycobiology 15(12):1320–1331

    Article  CAS  PubMed  Google Scholar 

  34. Lehri-Boufala S, Ouidja MO, Barbier-Chassefiere V, Henault E, Raisman-Vozari R, Garrigue-Antar L, Papy-Garcia D, Morin C (2015) New roles of glycosaminoglycans in alpha-synuclein aggregation in a cellular model of Parkinson disease. PLoS One 10(1):e0116641

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Mehra S, Ghosh D, Kumar R, Mondal M, Gadhe LG, Das S, Anoop A, Jha NN et al (2018) Glycosaminoglycans have variable effects on alpha-synuclein aggregation and differentially affect the activities of the resulting amyloid fibrils. J Biol Chem 293(34):12975–12991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Raghunathan R, Polinski NK, Klein JA, Hogan JD, Shao C, Khatri K, Leon D, McComb ME et al (2018) Glycomic and proteomic changes in aging brain Nigrostriatal pathway. Mol Cell Proteomics 17(9):1778–1787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Choudhary S, Save SN, Vavilala SL (2018) Unravelling the inhibitory activity of Chlamydomonas reinhardtii sulfated polysaccharides against alpha-Synuclein fibrillation. Sci Rep 8(1):5692

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Panigrahi GP, Rane AR, Vavilala SL, Choudhary S (2019) Deciphering the anti-Parkinson’s activity of sulphated polysaccharides from Chlamydomonas reinhardtii on the alpha-Synuclein mutants A30P, A53T, E46K, E57K and E35K. J Biochem 166(6):463–474

    Article  PubMed  Google Scholar 

  39. Yang X, Qian K (2017) Protein O-GlcNAcylation: emerging mechanisms and functions. Nat Rev Mol Cell Biol 18(7):452–465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Wani WY, Ouyang X, Benavides GA, Redmann M, Cofield SS, Shacka JJ, Chatham JC, Darley-Usmar V et al (2017) O-GlcNAc regulation of autophagy and alpha-synuclein homeostasis; implications for Parkinson’s disease. Mol Brain 10(1):32

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Levine PM, Galesic A, Balana AT, Mahul-Mellier AL, Navarro MX, De Leon CA, Lashuel HA, Pratt MR (2019) Alpha-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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Sidransky E, Nalls MA, Aasly JO, Aharon-Peretz J, Annesi G, Barbosa ER, Bar-Shira A, Berg D et al (2009) Multicenter analysis of glucocerebrosidase mutations in Parkinson’s disease. N Engl J Med 361(17):1651–1661

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Wong YC, Krainc D (2016) Lysosomal trafficking defects link Parkinson’s disease with Gaucher’s disease. Mov Disord 31(11):1610–1618

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Riboldi GM, Di Fonzo AB (2019) GBA, Gaucher Disease, and Parkinson’s disease: from genetic to clinic to new therapeutic approaches. Cells 8(4):E364

  45. Mullin S, Hughes D, Mehta A, Schapira AHV (2019) Neurological effects of glucocerebrosidase gene mutations. Eur J Neurol 26(3):388–e29

    Article  CAS  PubMed  Google Scholar 

  46. Platt FM, d'Azzo A, Davidson BL, Neufeld EF, Tifft CJ (2018) Lysosomal storage diseases. Nat Rev Dis Primers 4(1):27

    Article  PubMed  Google Scholar 

  47. Gegg ME, Schapira AHV (2018) The role of glucocerebrosidase in Parkinson disease pathogenesis. FEBS J 285(19):3591–3603

    Article  CAS  PubMed  Google Scholar 

  48. Papadopoulos VE, Nikolopoulou G, Antoniadou I, Karachaliou A, Arianoglou G, Emmanouilidou E, Sardi SP, Stefanis L et al (2018) Modulation of beta-glucocerebrosidase increases alpha-synuclein secretion and exosome release in mouse models of Parkinson’s disease. Hum Mol Genet 27(10):1696–1710

    CAS  PubMed  Google Scholar 

  49. Lin G, Wang L, Marcogliese PC, Bellen HJ (2019) Sphingolipids in the pathogenesis of Parkinson’s disease and parkinsonism. Trends Endocrinol Metab 30(2):106–117

    Article  CAS  PubMed  Google Scholar 

  50. Indellicato R, Trinchera M (2019) The link between Gaucher disease and Parkinson’sdDisease sheds light on old and novel disorders of sphingolipid metabolism. Int J Mol Sci 20(13):E3304

  51. Pchelina S, Baydakova G, Nikolaev M, Senkevich K, Emelyanov A, Kopytova A, Miliukhina I, Yakimovskii A et al (2018) Blood lysosphingolipids accumulation in patients with Parkinson’s disease with glucocerebrosidase 1 mutations. Mov Disord 33(8):1325–1330

    Article  CAS  PubMed  Google Scholar 

  52. Li H, Ham A, Ma TC, Kuo SH, Kanter E, Kim D, Ko HS, Quan Y et al (2019) Mitochondrial dysfunction and mitophagy defect triggered by heterozygous GBA mutations. Autophagy 15(1):113–130

    Article  CAS  PubMed  Google Scholar 

  53. Wilke M, Dornelles AD, Schuh AS, Vairo FP, Basgalupp SP, Siebert M, Nalin T, Piltcher OB et al (2019) Evaluation of the frequency of non-motor symptoms of Parkinson’s disease in adult patients with Gaucher disease type 1. Orphanet J Rare Dis 14(1):103

    Article  PubMed  PubMed Central  Google Scholar 

  54. Avenali M, Toffoli M, Mullin S, McNeil A, Hughes DA, Mehta A, Blandini F, Schapira AHV (2019) Evolution of prodromal parkinsonian features in a cohort of GBA mutation-positive individuals: a 6-year longitudinal study. J Neurol Neurosurg Psychiatry 90(10):1091–1097

    Article  PubMed  Google Scholar 

  55. Huebecker M, Moloney EB, van der Spoel AC, Priestman DA, Isacson O, Hallett PJ, Platt FM (2019) Reduced sphingolipid hydrolase activities, substrate accumulation and ganglioside decline in Parkinson’s disease. Mol Neurodegener 14(1):40

    Article  PubMed  PubMed Central  Google Scholar 

  56. Blandini F, Cilia R, Cerri S, Pezzoli G, Schapira AHV, Mullin S, Lanciego JL (2019) Glucocerebrosidase mutations and synucleinopathies: toward a model of precision medicine. Mov Disord 34(1):9–21

    Article  PubMed  Google Scholar 

  57. Paciotti S, Gatticchi L, Beccari T, Parnetti L (2019) Lysosomal enzyme activities as possible CSF biomarkers of synucleinopathies. Clin Chim Acta 495:13–24

    Article  CAS  PubMed  Google Scholar 

  58. Moren C, Juarez-Flores DL, Chau KY, Gegg M, Garrabou G, Gonzalez-Casacuberta I, Guitart-Mampel M, Tolosa E et al (2019) GBA mutation promotes early mitochondrial dysfunction in 3D neurosphere models. Aging (Albany NY) 11(22):10338–10355

    Article  CAS  Google Scholar 

  59. Romero R, Ramanathan A, Yuen T, Bhowmik D, Mathew M, Munshi LB, Javaid S, Bloch M et al (2019) Mechanism of glucocerebrosidase activation and dysfunction in Gaucher disease unraveled by molecular dynamics and deep learning. Proc Natl Acad Sci U S A 116(11):5086–5095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Lerche S, Wurster I, Roeben B, Zimmermann M, Riebenbauer B, Deuschle C, Hauser AK, Schulte C et al (2019) Parkinson’s disease: Glucocerebrosidase 1 mutation severity is associated with CSF alpha-synuclein profiles. Mov Disord 35(3):495–499

  61. Hertz E, Thornqvist M, Holmberg B, Machaczka M, Sidransky E, Svenningsson P (2019) First Clinicogenetic description of Parkinson’s disease related to GBA mutation S107L. Mov Disord Clin Pract 6(3):254–258

    Article  PubMed  PubMed Central  Google Scholar 

  62. Velez-Pardo C, Lorenzo-Betancor O, Jimenez-Del-Rio M, Moreno S, Lopera F, Cornejo-Olivas M, Torres L, Inca-Martinez M et al (2019) The distribution and risk effect of GBA variants in a large cohort of PD patients from Colombia and Peru. Parkinsonism Relat Disord 63:204–208

    Article  PubMed  PubMed Central  Google Scholar 

  63. Mahungu AC, Anderson DG, Rossouw AC, van Coller R, Carr JA, Ross OA, Bardien S (2019) Screening of the glucocerebrosidase (GBA) gene in south Africans of African ancestry with Parkinson’s disease. Neurobiol Aging

  64. Ji S, Wang C, Qiao H, Gu Z, Gan-Or Z, Fon EA, Chan P (2020) Decreased penetrance of Parkinson’s disease in elderly carriers of Glucocerebrosidase gene L444P/R mutations: a community-based 10-year longitudinal study. Mov Disord 35:672–678

    Article  CAS  PubMed  Google Scholar 

  65. Lin CH, Chen PL, Tai CH, Lin HI, Chen CS, Chen ML, Wu RM (2019) A clinical and genetic study of early-onset and familial parkinsonism in Taiwan: an integrated approach combining gene dosage analysis and next-generation sequencing. Mov Disord 34(4):506–515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Simuni T, Brumm MC, Uribe L, Caspell-Garcia C, Coffey CS, Siderowf A, Alcalay RN, Trojanowski JQ et al (2020) Clinical and dopamine transporter imaging characteristics of leucine-rich repeat kinase 2 (LRRK2) and glucosylceramidase beta (GBA) Parkinson’s disease participants in the Parkinson’s progression markers initiative: a dross-sectional study. Mov Disord. https://doi.org/10.1002/mds.27989

  67. Goldstein O, Gana-Weisz M, Cohen-Avinoam D, Shiner T, Thaler A, Cedarbaum JM, John S, Lalioti M et al (2019) Revisiting the non-Gaucher-GBA-E326K carrier state: Is it sufficient to increase Parkinson’s disease risk? Mol Genet Metab 128(4):470–475

    Article  CAS  PubMed  Google Scholar 

  68. Hsieh PC, Wang CC, Tsai CL, Yeh YM, Lee YS, Wu YR (2019) POLG R964C and GBA L444P mutations in familial Parkinson’s disease: case report and literature review. Brain Behav 9(5):e01281

    Article  PubMed  PubMed Central  Google Scholar 

  69. Sanyal A, DeAndrade MP, Novis HS, Lin S, Chang J, Lengacher N, Tomlinson JJ, Tansey MG et al (2020) Lysosome and inflammatory defects in GBA1-mutant astrocytes are normalized by LRRK2 inhibition. Mov Disord. https://doi.org/10.1002/mds.27994

  70. Gustavsson N, Marote A, Pomeshchik Y, Russ K, Azevedo C, Chumarina M, Goldwurm S, Collin A et al (2019) Generation of an induced pluripotent stem cell line (CSC-46) from a patient with Parkinson’s disease carrying a novel p.R301C mutation in the GBA gene. Stem Cell Res 34:101373

    Article  CAS  PubMed  Google Scholar 

  71. Rodriguez-Traver E, Rodriguez C, Diaz-Guerra E, Arenas F, Arauzo-Bravo M, Orera M, Kulisevsky J, Moratalla R et al (2019) Generation of an integration-free iPSC line, ICCSICi005-a, derived from a Parkinson’s disease patient carrying the L444P mutation in the GBA1 gene. Stem Cell Res 40:101578

    Article  CAS  PubMed  Google Scholar 

  72. Baden P, Yu C, Deleidi M (2019) Insights into GBA Parkinson’s disease pathology and therapy with induced pluripotent stem cell model systems. Neurobiol Dis 127:1–12

    Article  CAS  PubMed  Google Scholar 

  73. Chung SJ, Jeon S, Yoo HS, Kim G, Oh JS, Kim JS, Evans AC, Sohn YH et al (2019) Detrimental effect of type 2 diabetes mellitus in a large case series of Parkinson’s disease. Parkinsonism Relat Disord 64:54–59

    Article  PubMed  Google Scholar 

  74. Marques A, Dutheil F, Durand E, Rieu I, Mulliez A, Fantini ML, Boirie Y, Durif F (2018) Glucose dysregulation in Parkinson’s disease: too much glucose or not enough insulin? Parkinsonism Relat Disord 55:122–127

    Article  PubMed  Google Scholar 

  75. Konig A, Vicente Miranda H, Outeiro TF (2018) Alpha-synuclein glycation and the action of anti-diabetic agents in Parkinson’s disease. J Park Dis 8(1):33–43

    Google Scholar 

  76. Castellani R, Smith MA, Richey PL, Perry G (1996) Glycoxidation and oxidative stress in Parkinson disease and diffuse Lewy body disease. Brain Res 737(1–2):195–200

    Article  CAS  PubMed  Google Scholar 

  77. Guerrero E, Vasudevaraju P, Hegde ML, Britton GB, Rao KS (2013) Recent advances in alpha-synuclein functions, advanced glycation, and toxicity: implications for Parkinson’s disease. Mol Neurobiol 47(2):525–536

    Article  CAS  PubMed  Google Scholar 

  78. Trezzi JP, Galozzi S, Jaeger C, Barkovits K, Brockmann K, Maetzler W, Berg D, Marcus K et al (2017) Distinct metabolomic signature in cerebrospinal fluid in early Parkinson’s disease. Mov Disord 32(10):1401–1408

    Article  CAS  PubMed  Google Scholar 

  79. Biosa A, Sandrelli F, Beltramini M, Greggio E, Bubacco L, Bisaglia M (2017) Recent findings on the physiological function of DJ-1: beyond Parkinson’s disease. Neurobiol Dis 108:65–72

    Article  CAS  PubMed  Google Scholar 

  80. Sharma N, Rao SP, Kalivendi SV (2019) The deglycase activity of DJ-1 mitigates alpha-synuclein glycation and aggregation in dopaminergic cells: Role of oxidative stress mediated downregulation of DJ-1 in Parkinson’s disease. Free Radic Biol Med 135:28–37

    Article  CAS  PubMed  Google Scholar 

  81. Lee HJ, Yoon YS, Lee SJ (2018) Mechanism of neuroprotection by trehalose: controversy surrounding autophagy induction. Cell Death Dis 9(7):712

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Hoffmann AC, Minakaki G, Menges S, Salvi R, Savitskiy S, Kazman A, Vicente Miranda H, Mielenz D et al (2019) Extracellular aggregated alpha synuclein primarily triggers lysosomal dysfunction in neural cells prevented by trehalose. Sci Rep 9(1):544

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Varki A, Cummings RD, Aebi M, Packer NH, Seeberger PH, Esko JD, Stanley P, Hart G et al (2015) Symbol nomenclature for graphical representations of glycans. Glycobiology 25(12):1323–1324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported by “Aldo Ravelli” Center for Neurotechnology and Experimental Brain Therapeutics (to AM, PS, AC, RG, MT) and from the University of Insubria (to MT). AZ was supported by Fondazione Veronesi, Milan Italy. AM is a fellowship of “Aldo Ravelli” Center for Neurotechnology and Experimental Brain Therapeutics.

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Authors and Affiliations

  1. Department of Health Sciences, University of Milan, via Antonio di Rudinì 8, 20142, Milan, Italy

    Aida Zulueta, Paola Signorelli, Anna Caretti & Riccardo Ghidoni

  2. ”Aldo Ravelli” Center for Neurotechnology and Experimental Brain Therapeutics, via Antonio di Rudinì 8, 20142, Milan, Italy

    Alessandra Mingione, Paola Signorelli, Anna Caretti, Riccardo Ghidoni & Marco Trinchera

  3. Department of Medicine and Surgery, University of Insubria, via JH Dunant 5, 21100, Varese, Italy

    Marco Trinchera

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  1. Aida Zulueta
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  2. Alessandra Mingione
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AZ and AM conducted the literature search, AC made the tables and figure, MT wrote the manuscript and supervised the project, and PS, AC, and RG critically revised the manuscript. All authors have seen and approved the final version of the manuscript.

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Correspondence to Marco Trinchera.

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Zulueta, A., Mingione, A., Signorelli, P. et al. Simple and Complex Sugars in Parkinson’s Disease: a Bittersweet Taste. Mol Neurobiol 57, 2934–2943 (2020). https://doi.org/10.1007/s12035-020-01931-4

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