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Molecular Neurobiology

, Volume 55, Issue 11, pp 8754–8763 | Cite as

Diabetes Mellitus as a Risk Factor for Parkinson’s Disease: a Molecular Point of View

  • Alice Biosa
  • Tiago F. Outeiro
  • Luigi Bubacco
  • Marco Bisaglia
Article

Abstract

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by elevated concentrations of glucose in the blood. The chronic hyperglycemic state accounts for most of the vascular complications associated to the disease and the prevalent mechanism proposed is related to the glycating chemistry mediated by methylglyoxal (MG), which accumulates in T2DM. In recent years, a higher risk of Parkinson’s disease (PD) onset in people affected by T2DM has become evident, but the molecular mechanisms underlying the interplay between T2DM and PD are still unknown. The oxidative chemistry of dopamine and its reactivity towards the protein α-Synuclein (aS) has been associated to the pathogenesis of PD. Recently, aS has also been described to interact with MG. Interestingly, MG and the dopamine oxidation products share both structural similarity and chemical reactivity. The ability of MG to spread over the site of its production and react with aS could represent the rationale to explain the higher incidence of PD in T2DM-affected people and may open opportunities for the development of novel strategies to antagonize the raise of PD.

Keywords

α-Synuclein Type 2 diabetes mellitus Dopamine DOPAL Methylglyoxal Parkinson’s disease 

Notes

Funding Information

The study is supported by a grant from the Italian Ministry of Education, University and Research (2015T778JW). TFO is supported by the DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB). The study is also supported through a project co-funded by the Federal Ministry of Education and Research (BLMB) and the EU Joint programme-Neurodegenerative Disease Research (JPND) (aSynProtec).

References

  1. 1.
    Daneman D (2006) Type 1 diabetes. Lancet 367(9513):847–858.  https://doi.org/10.1016/S0140-6736(06)68341-4 CrossRefPubMedGoogle Scholar
  2. 2.
    Chatterjee S, Khunti K, Davies MJ (2017) Type 2 diabetes. Lancet 389(10085):2239–2251.  https://doi.org/10.1016/S0140-6736(17)30058-2 CrossRefPubMedGoogle Scholar
  3. 3.
    Mirghani Dirar A, Doupis J (2017) Gestational diabetes from A to Z. World J Diabetes 8(12):489–511.  https://doi.org/10.4239/wjd.v8.i12.489 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Cowie CC, Rust KF, Byrd-Holt DD, Eberhardt MS, Flegal KM, Engelgau MM, Saydah SH, Williams DE et al (2006) Prevalence of diabetes and impaired fasting glucose in adults in the U.S. population: National Health and Nutrition Examination Survey 1999–2002. Diabetes Care 29(6):1263–1268.  https://doi.org/10.2337/dc06-0062 CrossRefGoogle Scholar
  5. 5.
    Zimmet P, Alberti KG, Shaw J (2001) Global and societal implications of the diabetes epidemic. Nature 414(6865):782–787.  https://doi.org/10.1038/414782a CrossRefPubMedGoogle Scholar
  6. 6.
    Shamsaldeen YA, Mackenzie LS, Lione LA, Benham CD (2016) Methylglyoxal, a metabolite increased in diabetes is associated with insulin resistance, vascular dysfunction and neuropathies. Curr Drug Metab 17(4):359–367CrossRefGoogle Scholar
  7. 7.
    Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P (2006) Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol 5(1):64–74.  https://doi.org/10.1016/S1474-4422(05)70284-2 CrossRefPubMedGoogle Scholar
  8. 8.
    Biessels GJ, Strachan MW, Visseren FL, Kappelle LJ, Whitmer RA (2014) Dementia and cognitive decline in type 2 diabetes and prediabetic stages: towards targeted interventions. Lancet Diabetes Endocrinol 2(3):246–255.  https://doi.org/10.1016/S2213-8587(13)70088-3 CrossRefPubMedGoogle Scholar
  9. 9.
    Ott A, Stolk RP, Hofman A, van Harskamp F, Grobbee DE, Breteler MM (1996) Association of diabetes mellitus and dementia: the Rotterdam Study. Diabetologia 39(11):1392–1397CrossRefGoogle Scholar
  10. 10.
    Leibson CL, Rocca WA, Hanson VA, Cha R, Kokmen E, O'Brien PC, Palumbo PJ (1997) Risk of dementia among persons with diabetes mellitus: a population-based cohort study. Am J Epidemiol 145(4):301–308CrossRefGoogle Scholar
  11. 11.
    Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM (1999) Diabetes mellitus and the risk of dementia: the Rotterdam Study. Neurology 53(9):1937–1942CrossRefGoogle Scholar
  12. 12.
    Verdile G, Fuller SJ, Martins RN (2015) The role of type 2 diabetes in neurodegeneration. Neurobiol Dis 84:22–38.  https://doi.org/10.1016/j.nbd.2015.04.008 CrossRefPubMedGoogle Scholar
  13. 13.
    Kandimalla R, Thirumala V, Reddy PH (2017) Is Alzheimer’s disease a type 3 diabetes? A critical appraisal. Biochim Biophys Acta 1863(5):1078–1089.  https://doi.org/10.1016/j.bbadis.2016.08.018 CrossRefGoogle Scholar
  14. 14.
    Wijesekara N, Goncalves RA, De Felice FG, Fraser PE (2017) Impaired peripheral glucose homeostasis and Alzheimer’s disease. Neuropharmacology.  https://doi.org/10.1016/j.neuropharm.2017.11.027 CrossRefGoogle Scholar
  15. 15.
    de Nazareth AM (2017) Type 2 diabetes mellitus in the pathophysiology of Alzheimer’s disease. Dement Neuropsychol 11(2):105–113.  https://doi.org/10.1590/1980-57642016dn11-020002 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Kimura N (2016) Diabetes mellitus induces Alzheimer’s disease pathology: histopathological evidence from animal models. Int J Mol Sci 17(4):503.  https://doi.org/10.3390/ijms17040503 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Vieira MNN, Lima-Filho RAS, De Felice FG (2017) Connecting Alzheimer’s disease to diabetes: underlying mechanisms and potential therapeutic targets. Neuropharmacology.  https://doi.org/10.1016/j.neuropharm.2017.11.014 CrossRefGoogle Scholar
  18. 18.
    Plotegher N, Greggio E, Bisaglia M, Bubacco L (2014) Biophysical groundwork as a hinge to unravel the biology of alpha-synuclein aggregation and toxicity. Q Rev Biophys 47:1):1–1)48.  https://doi.org/10.1017/S0033583513000097 CrossRefPubMedGoogle Scholar
  19. 19.
    Hernandez DG, Reed X, Singleton AB (2016) Genetics in Parkinson disease: Mendelian versus non-Mendelian inheritance. J Neurochem 139 Suppl 1:59–74.  https://doi.org/10.1111/jnc.13593 CrossRefPubMedGoogle Scholar
  20. 20.
    Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H et al (1997) Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 276(5321):2045–2047CrossRefGoogle Scholar
  21. 21.
    Boni-Schnetzler M, Thorne J, Parnaud G, Marselli L, Ehses JA, Kerr-Conte J, Pattou F, Halban PA et al (2008) Increased interleukin (IL)-1beta messenger ribonucleic acid expression in beta -cells of individuals with type 2 diabetes and regulation of IL-1beta in human islets by glucose and autostimulation. J Clin Endocrinol Metab 93(10):4065–4074.  https://doi.org/10.1210/jc.2008-0396 CrossRefGoogle Scholar
  22. 22.
    Greggio E, Civiero L, Bisaglia M, Bubacco L (2012) Parkinson’s disease and immune system: is the culprit LRRKing in the periphery? J Neuroinflammation 9:94.  https://doi.org/10.1186/1742-2094-9-94 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Friederich M, Hansell P, Palm F (2009) Diabetes, oxidative stress, nitric oxide and mitochondria function. Curr Diabetes Rev 5(2):120–144CrossRefGoogle Scholar
  24. 24.
    Henchcliffe C, Beal MF (2008) Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis. Nat Clin Pract Neurol 4(11):600–609.  https://doi.org/10.1038/ncpneuro0924 CrossRefPubMedGoogle Scholar
  25. 25.
    Santiago JA, Potashkin JA (2013) Shared dysregulated pathways lead to Parkinson’s disease and diabetes. Trends Mol Med 19(3):176–186.  https://doi.org/10.1016/j.molmed.2013.01.002 CrossRefPubMedGoogle Scholar
  26. 26.
    Hu G, Jousilahti P, Bidel S, Antikainen R, Tuomilehto J (2007) Type 2 diabetes and the risk of Parkinson’s disease. Diabetes Care 30(4):842–847.  https://doi.org/10.2337/dc06-2011 CrossRefPubMedGoogle Scholar
  27. 27.
    Xu Q, Park Y, Huang X, Hollenbeck A, Blair A, Schatzkin A, Chen H (2011) Diabetes and risk of Parkinson’s disease. Diabetes Care 34(4):910–915.  https://doi.org/10.2337/dc10-1922 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Schernhammer E, Hansen J, Rugbjerg K, Wermuth L, Ritz B (2011) Diabetes and the risk of developing Parkinson’s disease in Denmark. Diabetes Care 34(5):1102–1108.  https://doi.org/10.2337/dc10-1333 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Sun Y, Chang YH, Chen HF, Su YH, Su HF, Li CY (2012) Risk of Parkinson disease onset in patients with diabetes: s9-year population-based cohort study with age and sex stratifications. Diabetes Care 35(5):1047–1049.  https://doi.org/10.2337/dc11-1511 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Yang YW, Hsieh TF, Li CI, Liu CS, Lin WY, Chiang JH, Li TC, Lin CC (2017) Increased risk of Parkinson disease with diabetes mellitus in a population-based study. Medicine (Baltimore) 96(3):e5921 00005792-201701200-00030CrossRefGoogle Scholar
  31. 31.
    Yue X, Li H, Yan H, Zhang P, Chang L, Li T (2016) Risk of Parkinson disease in diabetes mellitus: an updated meta-analysis of population-based cohort studies. Medicine (Baltimore) 95(18):e3549.  https://doi.org/10.1097/MD.0000000000003549 CrossRefGoogle Scholar
  32. 32.
    Voziyan P, Brown KL, Chetyrkin S, Hudson B (2014) Site-specific AGE modifications in the extracellular matrix: a role for glyoxal in protein damage in diabetes. Clin Chem Lab Med 52(1):39–45.  https://doi.org/10.1515/cclm-2012-0818 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Ahmed N, Thornalley PJ (2007) Advanced glycation endproducts: what is their relevance to diabetic complications? Diabetes Obes Metab 9(3):233–245.  https://doi.org/10.1111/j.1463-1326.2006.00595.x CrossRefPubMedGoogle Scholar
  34. 34.
    Rabbani N, Thornalley PJ (2015) Dicarbonyl stress in cell and tissue dysfunction contributing to ageing and disease. Biochem Biophys Res Commun 458(2):221–226.  https://doi.org/10.1016/j.bbrc.2015.01.140 CrossRefPubMedGoogle Scholar
  35. 35.
    Lo TW, Westwood ME, McLellan AC, Selwood T, Thornalley PJ (1994) Binding and modification of proteins by methylglyoxal under physiological conditions. A kinetic and mechanistic study with N alpha-acetylarginine, N alpha-acetylcysteine, and N alpha-acetyllysine, and bovine serum albumin. J Biol Chem 269(51):32299–32305PubMedGoogle Scholar
  36. 36.
    Knott HM, Brown BE, Davies MJ, Dean RT (2003) Glycation and glycoxidation of low-density lipoproteins by glucose and low-molecular mass aldehydes. Formation of modified and oxidized particles. Eur J Biochem 270(17):3572–3582PubMedGoogle Scholar
  37. 37.
    Rabbani N, Thornalley PJ (2014) The critical role of methylglyoxal and glyoxalase 1 in diabetic nephropathy. Diabetes 63(1):50–52.  https://doi.org/10.2337/db13-1606 CrossRefPubMedGoogle Scholar
  38. 38.
    Lu J, Randell E, Han Y, Adeli K, Krahn J, Meng QH (2011) Increased plasma methylglyoxal level, inflammation, and vascular endothelial dysfunction in diabetic nephropathy. Clin Biochem 44(4):307–311.  https://doi.org/10.1016/j.clinbiochem.2010.11.004 CrossRefPubMedGoogle Scholar
  39. 39.
    McLellan AC, Thornalley PJ, Benn J, Sonksen PH (1994) Glyoxalase system in clinical diabetes mellitus and correlation with diabetic complications. Clin Sci (Lond) 87(1):21–29CrossRefGoogle Scholar
  40. 40.
    Kalapos MP (1994) Methylglyoxal toxicity in mammals. Toxicol Lett 73(1):3–24CrossRefGoogle Scholar
  41. 41.
    Rabbani N, Thornalley PJ (2012) Methylglyoxal, glyoxalase 1 and the dicarbonyl proteome. Amino Acids 42(4):1133–1142.  https://doi.org/10.1007/s00726-010-0783-0 CrossRefPubMedGoogle Scholar
  42. 42.
    Vicente Miranda H, Szego EM, Oliveira LM, Breda C, Darendelioglu E, de Oliveira RM, Ferreira DG, Gomes MA et al (2017) Glycation potentiates alpha-synuclein-associated neurodegeneration in synucleinopathies. Brain 140:1399–1419.  https://doi.org/10.1093/brain/awx056 CrossRefPubMedGoogle Scholar
  43. 43.
    Jia X, Olson DJ, Ross AR, Wu L (2006) Structural and functional changes in human insulin induced by methylglyoxal. FASEB J 20(9):1555–1557.  https://doi.org/10.1096/fj.05-5478fje CrossRefPubMedGoogle Scholar
  44. 44.
    Jia X, Wu L (2007) Accumulation of endogenous methylglyoxal impaired insulin signaling in adipose tissue of fructose-fed rats. Mol Cell Biochem 306(1–2):133–139.  https://doi.org/10.1007/s11010-007-9563-x CrossRefPubMedGoogle Scholar
  45. 45.
    Sulzer D, Surmeier DJ (2013) Neuronal vulnerability, pathogenesis, and Parkinson’s disease. Mov Disord 28(6):715–724.  https://doi.org/10.1002/mds.25187 CrossRefPubMedGoogle Scholar
  46. 46.
    Surmeier DJ, Obeso JA, Halliday GM (2017) Selective neuronal vulnerability in Parkinson disease. Nat Rev Neurosci 18(2):101–113.  https://doi.org/10.1038/nrn.2016.178 CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Bisaglia M, Greggio E, Beltramini M, Bubacco L (2013) Dysfunction of dopamine homeostasis: clues in the hunt for novel Parkinson’s disease therapies. FASEB J 27(6):2101–2110.  https://doi.org/10.1096/fj.12-226852 CrossRefPubMedGoogle Scholar
  48. 48.
    Mosharov EV, Larsen KE, Kanter E, Phillips KA, Wilson K, Schmitz Y, Krantz DE, Kobayashi K et al (2009) Interplay between cytosolic dopamine, calcium, and alpha-synuclein causes selective death of substantia nigra neurons. Neuron 62(2):218–229.  https://doi.org/10.1016/j.neuron.2009.01.033 CrossRefGoogle Scholar
  49. 49.
    Zucca FA, Segura-Aguilar J, Ferrari E, Munoz P, Paris I, Sulzer D, Sarna T, Casella L et al (2017) Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson’s disease. Prog Neurobiol 155:96–119.  https://doi.org/10.1016/j.pneurobio.2015.09.012 CrossRefGoogle Scholar
  50. 50.
    Bisaglia M, Filograna R, Beltramini M, Bubacco L (2014) Are dopamine derivatives implicated in the pathogenesis of Parkinson’s disease? Ageing Res Rev 13:107–114.  https://doi.org/10.1016/j.arr.2013.12.009 CrossRefPubMedGoogle Scholar
  51. 51.
    LaVoie MJ, Ostaszewski BL, Weihofen A, Schlossmacher MG, Selkoe DJ (2005) Dopamine covalently modifies and functionally inactivates parkin. Nat Med 11(11):1214–1221.  https://doi.org/10.1038/nm1314 CrossRefPubMedGoogle Scholar
  52. 52.
    Bisaglia M, Tosatto L, Munari F, Tessari I, de Laureto PP, Mammi S, Bubacco L (2010) Dopamine quinones interact with alpha-synuclein to form unstructured adducts. Biochem Biophys Res Commun 394(2):424–428.  https://doi.org/10.1016/j.bbrc.2010.03.044 CrossRefPubMedGoogle Scholar
  53. 53.
    Girotto S, Sturlese M, Bellanda M, Tessari I, Cappellini R, Bisaglia M, Bubacco L, Mammi S (2012) Dopamine-derived quinones affect the structure of the redox sensor DJ-1 through modifications at Cys-106 and Cys-53. J Biol Chem 287(22):18738–18749.  https://doi.org/10.1074/jbc.M111.311589 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Conway KA, Rochet JC, Bieganski RM, Lansbury PT Jr (2001) Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct. Science 294(5545):1346–1349.  https://doi.org/10.1126/science.1063522 CrossRefPubMedGoogle Scholar
  55. 55.
    Norris EH, Giasson BI, Hodara R, Xu S, Trojanowski JQ, Ischiropoulos H, Lee VM (2005) Reversible inhibition of alpha-synuclein fibrillization by dopaminochrome-mediated conformational alterations. J Biol Chem 280(22):21212–21219.  https://doi.org/10.1074/jbc.M412621200 CrossRefPubMedGoogle Scholar
  56. 56.
    Cappai R, Leck SL, Tew DJ, Williamson NA, Smith DP, Galatis D, Sharples RA, Curtain CC et al (2005) Dopamine promotes alpha-synuclein aggregation into SDS-resistant soluble oligomers via a distinct folding pathway. FASEB J 19(10):1377–1379.  https://doi.org/10.1096/fj.04-3437fje CrossRefGoogle Scholar
  57. 57.
    Mazzulli JR, Armakola M, Dumoulin M, Parastatidis I, Ischiropoulos H (2007) Cellular oligomerization of alpha-synuclein is determined by the interaction of oxidized catechols with a C-terminal sequence. J Biol Chem 282(43):31621–31630.  https://doi.org/10.1074/jbc.M704737200 CrossRefPubMedGoogle Scholar
  58. 58.
    Outeiro TF, Klucken J, Bercury K, Tetzlaff J, Putcha P, Oliveira LM, Quintas A, McLean PJ et al (2009) Dopamine-induced conformational changes in alpha-synuclein. PLoS One 4(9):e6906.  https://doi.org/10.1371/journal.pone.0006906 CrossRefGoogle Scholar
  59. 59.
    Bisaglia M, Mammi S, Bubacco L (2007) Kinetic and structural analysis of the early oxidation products of dopamine: analysis of the interactions with alpha-synuclein. J Biol Chem 282(21):15597–15605.  https://doi.org/10.1074/jbc.M610893200 CrossRefPubMedGoogle Scholar
  60. 60.
    Bisaglia M, Soriano ME, Arduini I, Mammi S, Bubacco L (2010) Molecular characterization of dopamine-derived quinones reactivity toward NADH and glutathione: implications for mitochondrial dysfunction in Parkinson disease. Biochim Biophys Acta 1802(9):699–706.  https://doi.org/10.1016/j.bbadis.2010.06.006 CrossRefPubMedGoogle Scholar
  61. 61.
    Casida JE, Ford B, Jinsmaa Y, Sullivan P, Cooney A, Goldstein DS (2014) Benomyl, aldehyde dehydrogenase, DOPAL, and the catecholaldehyde hypothesis for the pathogenesis of Parkinson’s disease. Chem Res Toxicol 27(8):1359–1361.  https://doi.org/10.1021/tx5002223 CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Fitzmaurice AG, Rhodes SL, Lulla A, Murphy NP, Lam HA, O'Donnell KC, Barnhill L, Casida JE et al (2013) Aldehyde dehydrogenase inhibition as a pathogenic mechanism in Parkinson disease. Proc Natl Acad Sci U S A 110(2):636–641.  https://doi.org/10.1073/pnas.1220399110 CrossRefGoogle Scholar
  63. 63.
    Wey MC, Fernandez E, Martinez PA, Sullivan P, Goldstein DS, Strong R (2012) Neurodegeneration and motor dysfunction in mice lacking cytosolic and mitochondrial aldehyde dehydrogenases: implications for Parkinson’s disease. PLoS One 7(2):e31522.  https://doi.org/10.1371/journal.pone.0031522 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Rees JN, Florang VR, Eckert LL, Doorn JA (2009) Protein reactivity of 3,4-dihydroxyphenylacetaldehyde, a toxic dopamine metabolite, is dependent on both the aldehyde and the catechol. Chem Res Toxicol 22(7):1256–1263.  https://doi.org/10.1021/tx9000557 CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Plotegher N, Bubacco L (2016) Lysines, Achilles’ heel in alpha-synuclein conversion to a deadly neuronal endotoxin. Ageing Res Rev 26:62–71.  https://doi.org/10.1016/j.arr.2015.12.002 CrossRefPubMedGoogle Scholar
  66. 66.
    Wilhelm BG, Mandad S, Truckenbrodt S, Krohnert K, Schafer C, Rammner B, Koo SJ, Classen GA et al (2014) Composition of isolated synaptic boutons reveals the amounts of vesicle trafficking proteins. Science 344(6187):1023–1028.  https://doi.org/10.1126/science.1252884 CrossRefGoogle Scholar
  67. 67.
    Bisaglia M, Mammi S, Bubacco L (2009) Structural insights on physiological functions and pathological effects of alpha-synuclein. FASEB J 23(2):329–340.  https://doi.org/10.1096/fj.08-119784 CrossRefPubMedGoogle Scholar
  68. 68.
    Burke WJ, Kumar VB, Pandey N, Panneton WM, Gan Q, Franko MW, O'Dell M, Li SW et al (2008) Aggregation of alpha-synuclein by DOPAL, the monoamine oxidase metabolite of dopamine. Acta Neuropathol 115(2):193–203.  https://doi.org/10.1007/s00401-007-0303-9 CrossRefGoogle Scholar
  69. 69.
    Jinsmaa Y, Sullivan P, Gross D, Cooney A, Sharabi Y, Goldstein DS (2014) Divalent metal ions enhance DOPAL-induced oligomerization of alpha-synuclein. Neurosci Lett 569:27–32.  https://doi.org/10.1016/j.neulet.2014.03.016 CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Follmer C, Coelho-Cerqueira E, Yatabe-Franco DY, Araujo GD, Pinheiro AS, Domont GB, Eliezer D (2015) Oligomerization and membrane-binding properties of covalent adducts formed by the interaction of alpha-synuclein with the toxic dopamine metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL). J Biol Chem 290(46):27660–27679.  https://doi.org/10.1074/jbc.M115.686584 CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Plotegher N, Berti G, Ferrari E, Tessari I, Zanetti M, Lunelli L, Greggio E, Bisaglia M et al (2017) DOPAL derived alpha-synuclein oligomers impair synaptic vesicles physiological function. Sci Rep 7:40699.  https://doi.org/10.1038/srep40699
  72. 72.
    Rabbani N, Thornalley PJ (2014) Measurement of methylglyoxal by stable isotopic dilution analysis LC-MS/MS with corroborative prediction in physiological samples. Nat Protoc 9(8):1969–1979.  https://doi.org/10.1038/nprot.2014.129 CrossRefPubMedGoogle Scholar
  73. 73.
    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):195–200CrossRefGoogle Scholar
  74. 74.
    Dalfo E, Portero-Otin M, Ayala V, Martinez A, Pamplona R, Ferrer I (2005) Evidence of oxidative stress in the neocortex in incidental Lewy body disease. J Neuropathol Exp Neurol 64(9):816–830CrossRefGoogle Scholar
  75. 75.
    Foretz M, Guigas B, Bertrand L, Pollak M, Viollet B (2014) Metformin: from mechanisms of action to therapies. Cell Metab 20(6):953–966.  https://doi.org/10.1016/j.cmet.2014.09.018 CrossRefPubMedGoogle Scholar
  76. 76.
    Wahlqvist ML, Lee MS, Hsu CC, Chuang SY, Lee JT, Tsai HN (2012) Metformin-inclusive sulfonylurea therapy reduces the risk of Parkinson’s disease occurring with type 2 diabetes in a Taiwanese population cohort. Parkinsonism Relat Disord 18(6):753–758.  https://doi.org/10.1016/j.parkreldis.2012.03.010 CrossRefPubMedGoogle Scholar
  77. 77.
    Patil SP, Jain PD, Ghumatkar PJ, Tambe R, Sathaye S (2014) Neuroprotective effect of metformin in MPTP-induced Parkinson’s disease in mice. Neuroscience 277:747–754.  https://doi.org/10.1016/j.neuroscience.2014.07.046 CrossRefPubMedGoogle Scholar
  78. 78.
    Lu M, Su C, Qiao C, Bian Y, Ding J, Hu G (2016) Metformin prevents dopaminergic neuron death in MPTP/P-induced mouse model of Parkinson’s disease via autophagy and mitochondrial ROS clearance. Int J Neuropsychopharmacol 19(9):pyw047.  https://doi.org/10.1093/ijnp/pyw047 CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Bayliss JA, Lemus MB, Santos VV, Deo M, Davies JS, Kemp BE, Elsworth JD, Andrews ZB (2016) Metformin prevents nigrostriatal dopamine degeneration independent of AMPK activation in dopamine neurons. PLoS One 11(7):e0159381.  https://doi.org/10.1371/journal.pone.0159381 CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Katila N, Bhurtel S, Shadfar S, Srivastav S, Neupane S, Ojha U, Jeong GS, Choi DY (2017) Metformin lowers alpha-synuclein phosphorylation and upregulates neurotrophic factor in the MPTP mouse model of Parkinson’s disease. Neuropharmacology 125:396–407.  https://doi.org/10.1016/j.neuropharm.2017.08.015 CrossRefPubMedGoogle Scholar
  81. 81.
    Canto C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, Elliott PJ, Puigserver P et al (2009) AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature 458(7241):1056–1060.  https://doi.org/10.1038/nature07813 CrossRefGoogle Scholar
  82. 82.
    Hardie DG (2011) AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function. Genes Dev 25(18):1895–1908.  https://doi.org/10.1101/gad.17420111 CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Beisswenger PJ, Howell SK, Touchette AD, Lal S, Szwergold BS (1999) Metformin reduces systemic methylglyoxal levels in type 2 diabetes. Diabetes 48(1):198–202CrossRefGoogle Scholar
  84. 84.
    Ruggiero-Lopez D, Lecomte M, Moinet G, Patereau G, Lagarde M, Wiernsperger N (1999) Reaction of metformin with dicarbonyl compounds. Possible implication in the inhibition of advanced glycation end product formation. Biochem Pharmacol 58(11):1765–1773CrossRefGoogle Scholar
  85. 85.
    Beisswenger P, Ruggiero-Lopez D (2003) Metformin inhibition of glycation processes. Diabetes Metab 29(4 Pt 2):6S95–6S6103CrossRefGoogle Scholar
  86. 86.
    zRabbani N, Xue M, Thornalley PJ (2016) Dicarbonyls and glyoxalase in disease mechanisms and clinical therapeutics. Glycoconj J 33(4):513–525.  https://doi.org/10.1007/s10719-016-9705-z CrossRefGoogle Scholar
  87. 87.
    Xue M, Rabbani N, Momiji H, Imbasi P, Anwar MM, Kitteringham N, Park BK, Souma T et al (2012) Transcriptional control of glyoxalase 1 by Nrf2 provides a stress-responsive defence against dicarbonyl glycation. Biochem J 443(1):213–222.  https://doi.org/10.1042/BJ20111648 CrossRefGoogle Scholar
  88. 88.
    Xue M, Weickert MO, Qureshi S, Kandala NB, Anwar A, Waldron M, Shafie A, Messenger D et al (2016) Improved glycemic control and vascular function in overweight and obese subjects by glyoxalase 1 inducer formulation. Diabetes 65(8):2282–2294.  https://doi.org/10.2337/db16-0153 CrossRefGoogle Scholar
  89. 89.
    Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, Dekker MC, Squitieri F et al (2003) Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299(5604):256–259.  https://doi.org/10.1126/science.1077209 CrossRefGoogle Scholar
  90. 90.
    Lee JY, Song J, Kwon K, Jang S, Kim C, Baek K, Kim J, Park C (2012) Human DJ-1 and its homologs are novel glyoxalases. Hum Mol Genet 21(14):3215–3225.  https://doi.org/10.1093/hmg/dds155 CrossRefPubMedGoogle Scholar
  91. 91.
    Richarme G, Mihoub M, Dairou J, Bui LC, Leger T, Lamouri A (2015) Parkinsonism-associated protein DJ-1/Park7 is a major protein deglycase that repairs methylglyoxal- and glyoxal-glycated cysteine, arginine, and lysine residues. J Biol Chem 290(3):1885–1897.  https://doi.org/10.1074/jbc.M114.597815 CrossRefPubMedGoogle Scholar
  92. 92.
    Richarme G, Liu C, Mihoub M, Abdallah J, Leger T, Joly N, Liebart JC, Jurkunas UV et al (2017) Guanine glycation repair by DJ-1/Park7 and its bacterial homologs. Science 357(6347):208–211.  https://doi.org/10.1126/science.aag1095 CrossRefGoogle Scholar
  93. 93.
    Zondler L, Miller-Fleming L, Repici M, Goncalves S, Tenreiro S, Rosado-Ramos R, Betzer C, Straatman KR et al (2014) DJ-1 interactions with alpha-synuclein attenuate aggregation and cellular toxicity in models of Parkinson’s disease. Cell Death Dis 5:e1350.  https://doi.org/10.1038/cddis.2014.307 CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Molecular Physiology and Biophysics Unit, Department of BiologyUniversity of PadovaPadovaItaly
  2. 2.Department of Experimental NeurodegenerationUniversity Medical Center GoettingenGoettingenGermany
  3. 3.Max Planck Institute for Experimental MedicineGoettingenGermany
  4. 4.Institute of Neuroscience, The Medical SchoolNewcastle UniversityNewcastle Upon TyneUK

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