Age- and brain region-dependent α-synuclein oligomerization is attributed to alterations in intrinsic enzymes regulating α-synuclein phosphorylation in aging monkey brains

Oncotarget

Volumn 7, Issue 8, 2016, Pages 8466-8480

  Chen, Min ^a,b   Yang, Weiwei ^a,b   Li, Xin ^a,b   Li, Xuran ^a,b   Wang, Peng ^a,b   Yue, Feng ^a,b   Yang, Hui ^b,c   Chan, Piu ^a,b,c   Yu, Shun ^a,b,c  

^a CAPITAL MEDICAL UNIVERSITY   (China)

^b BEIJING INSTITUTE FOR BRAIN DISORDERS   (China)

^c Beijing Key Laboratory for Parkinson's Disease   (China)

Author keywords

Aging; Brain; Gerotarget Section; Polo like kinase 2; Protein phosphatase 2A; synuclein

Indexed keywords

ALPHA SYNUCLEIN; CERAMIDE; PHOSPHOPROTEIN PHOSPHATASE 2A; POLO LIKE KINASE 2; GLUCOSYLCERAMIDASE; PHOSPHOPROTEIN PHOSPHATASE 2; PROTEIN SERINE THREONINE KINASE;

AGE; AGING; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BRAIN REGION; CEREBELLUM; CONTROLLED STUDY; CORPUS STRIATUM; CYTOTOXICITY; ENZYME ACTIVATION; ENZYME INHIBITION; HIPPOCAMPUS; NONHUMAN; OCCIPITAL CORTEX; OLIGOMERIZATION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; ANIMAL; APOPTOSIS; BRAIN; CELL PROLIFERATION; CHEMISTRY; LEWY BODY; MACACA FASCICULARIS; METABOLISM; PATHOLOGY; PHOSPHORYLATION; PHYSIOLOGY; PROTEIN MULTIMERIZATION; WESTERN BLOTTING;

AGING; ALPHA-SYNUCLEIN; ANIMALS; APOPTOSIS; BLOTTING, WESTERN; BRAIN; CELL PROLIFERATION; CERAMIDES; CORPUS STRIATUM; GLUCOSYLCERAMIDASE; HIPPOCAMPUS; LEWY BODIES; MACACA FASCICULARIS; PHOSPHORYLATION; PROTEIN MULTIMERIZATION; PROTEIN PHOSPHATASE 2; PROTEIN-SERINE-THREONINE KINASES;

EID: 84961620865     PISSN: None     EISSN: 19492553     Source Type: Journal    
DOI: 10.18632/oncotarget.6445     Document Type: Article

References (47)

1. Rodriguez M, Rodriguez-Sabate C, Morales I, Sanchez A, Sabate M. Parkinson's disease as a result of aging. Aging Cell. 2015; 14: 293-308
2. Hanson JC, Lippa CF. Lewy body dementia. Int Rev Neurobiol. 2009; 84: 215-228
3. Jellinger, KA. Alpha-synuclein pathology in Parkinson's and Alzheimer's disease brain: incidence and topographic distribution-a pilot study. Acta Neuropathol. 2003; 106: 191-201
4. Jellinger KA. Formation and development of Lewy pathology: a critical update. J Neurol. 2009; 256 Suppl 3: 270-279
5. Baba M, Nakajo S, Tu PH, Tomita T, Nakaya K, Lee, VM, TrojanowskiJQ, Iwatsubo T. Aggregation of alphasynuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies. Am J Pathol. 1998; 152: 879-884
6. Spillantini MG, Crowther RA, Jakes R, Hasegawa M, Goedert M. Alpha-synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with lewy bodies. Proc Natl Acad Sci U S A. 1998; 95: 6469-6473
7. Colla E, Jensen PH, Pletnikova O, Troncoso JC, Glabe C, Lee MK. Accumulation of toxic αsynuclein oligomer within endoplasmic reticulum occurs in alphasynucleinopathy in vivo. J Neurosci. 2012; 32: 3301-3305
8. Malchiodi-Albedi F, Paradisi S, Matteucci A, Frank C, Diociaiuti M. Amyloid oligomer neurotoxicity, calcium dysregulation, and lipid rafts. Int J Alzheimers Dis. 2011; 2011: 906-964
9. Volles MJ, Lansbury PT Jr. Zeroing in on the pathogenic form of alpha-synuclein and its mechanism of neurotoxicity in Parkinson's disease. Biochemistry. 2003; 42: 7871-7878
10. Winner B, Jappelli R, Maji SK, Desplats PA, Boyer L, Aigner S, Hetzer C, Loher T, Vilar M, Campioni S, Tzitzilonis C, Soragni A, Jessberger S, Mira H, Consiglio A, Pham E, Masliah E, Gage FH, Riek R. In vivo demonstration that alpha-synuclein oligomers are toxic. Proc Natl Acad Sci U S A. 2011; 108: 4194-4199
11. Outeiro TF, Putcha P, Tetzlaff JE, Spoelgen R, Koker M, Carvalho F, Hyman BT, McLean PJ. Formation of toxic oligomeric alpha-synuclein species in living cells. PLoS One. 2008; 3: e1867
12. Zhou W, Milder JB, Freed CR. Transgenic mice overexpressing tyrosine-to-cysteine mutant human alphasynuclein: a progressive neurodegenerative model of diffuse Lewy body disease. J Biol Chem. 2008; 283: 9863-9870
13. Cookson MR, van der Brug M. Cell systems and the toxic mechanism(s) of alpha-synuclein. Exp Neurol. 2008; 209: 5-11
14. Martin ZS, Neugebauer V, Dineley KT, Kayed R, Zhang W, Reese LC, Taglialatela G. αSynuclein oligomers oppose long-term potentiation and impair memory through a calcineurin-dependent mechanism: relevance to human synucleopathic diseases. J Neurochem. 2012; 120: 440-452
15. Choi BK, Choi MG, Kim JY, Yang Y, Lai Y, Kweon DH, Lee NK, Shin YK. Large alpha-synuclein oligomers inhibit neuronal SNARE-mediated vesicle docking. Proc Natl Acad Sci U S A. 2013; 110: 4087-4092
16. Kramer ML, Schulz-Schaeffer WJ. Presynaptic alpha-synuclein aggregates, not Lewy bodies, cause neurodegeneration in dementia with Lewy bodies. J Neurosci. 2007; 27: 1405-1410
17. Schulz-Schaeffer WJ. The synaptic pathology of alphasynuclein aggregation in dementia with Lewy bodies, Parkinson's disease and Parkinson's disease dementia. Acta Neuropathol. 2010; 120: 131-143
18. Chen M, Wang T, Yue F, Li X, Wang P, Li Y, Chan P, Yu S. Tea polyphenols alleviate motor impairments, dopaminergic neuronal injury, and cerebral αsynuclein aggregation in MPTP-intoxicated parkinsonian monkeys. Neuroscience. 2015; 286: 383-392
19. Zhou J, Broe M, Huang Y, Anderson JP, Gai WP, Milward EA, Porritt M, Howells D, Hughes AJ, Wang X, Halliday GM. Changes in the solubility and phosphorylation of a-synuclein over the course of Parkinson's disease. Acta Neuropathol. 2011; 121: 695-704
20. Smith WW, Margolis RL, Li X, Troncoso JC, Lee MK, Dawson VL, Dawson TM, Iwatsubo T, Ross CA. Alpha-synuclein phosphorylation enhances eosinophilic cytoplasmic inclusion formation in SH-SY5Y cells. J Neurosci. 2005; 25: 5544-5552
21. Arawaka S, Wada M, Goto S, Karube H, Sakamoto M, Ren CH, Koyama S, Nagasawa H, Kimura H, Kawanami T, Kurita K, Tajima K, Daimon M, et al. The role of G-protein-coupled receptor kinase 5 in pathogenesis of sporadic Parkinson's disease. J Neurosci. 2006; 26: 9227-9238
22. Kragh CL, Lund LB, Febbraro F, Hansen HD, Gai WP, El-Agnaf O, Richter-Landsberg C, Jensen PH. Alpha-synuclein aggregation and Ser-129 phosphorylation-dependent cell death in oligodendroglial cells. J Biol Chem. 2009; 284: 10211-10222
23. Inglis KJ, Chereau D, Brigham EF, Chiou SS, Schobel S, Frigon NL, Yu M, Caccavello RJ, Nelson S, Motter R, Wright S, Chian D, Santiago P, et al. Polo-like kinase 2 (PLK2) phosphorylates alpha-synuclein at serine 129 in central nervous system. J Biol Chem. 2009; 284: 2598-2602
24. Bergeron M, Motter R, Tanaka P, Fauss D, Babcock M, Chiou SS, Nelson S, San Pablo F, Anderson JP. In vivo modulation of polo-like kinases supports a key role for PLK2 in Ser129 αsynuclein phosphorylation in mouse brain. Neuroscience. 2014; 256: 72-82
25. Aubele DL, Hom RK, Adler M, Galemmo RA Jr, Bowers S, Truong AP, Pan H, Beroza P, Neitz RJ, Yao N, Lin M, Tonn G, Zhang H, et al. Selective and brain-permeable pololike kinase-2 (Plk-2) inhibitors that reduce αsynuclein phosphorylation in rat brain. Chem Med Chem. 2013; 8: 1295-1313
26. Mbefo MK, Paleologou KE, Boucharaba A, Oueslati A, Schell H, Fournier M, Olschewski D, Yin G, Zweckstetter M, Masliah E, Kahle PJ, Hirling H, Lashuel HA. Phosphorylation of synucleins by members of the Polo-like kinase family. J Biol Chem. 2010; 285: 2807-2822
27. Wu J, Lou H, Alerte TN, Stachowski EK, Chen J, Singleton AB, Hamilton RL, Perez RG. Lewy-like aggregation of a-synuclein reduces protein phosphatase 2A activity in vitro and in vivo. Neuroscience. 2012; 207: 288-297
28. Pérez-Revuelta BI, Hettich MM, Ciociaro A, Rotermund C, Kahle PJ, Krauss S, Di Monte DA. Metformin lowers Ser-129 phosphorylated αsynuclein levels via mTORdependent protein phosphatase 2A activation. Cell Death Dis. 2014; 5: e1209
29. Lee KW, Chen W, Junn E, Im JY, Grosso H, Sonsalla PK, Feng X, Ray N, Fernandez JR, Chao Y, Masliah E, Voronkov M, Braithwaite SP, et al. Enhanced phosphatase activity attenuates αsynucleinopathy in a mouse model. J Neurosci. 2011; 31: 6963-6971
30. Wu J, Lou H, Alerte TN, Stachowski EK, Chen J, Singleton AB, Hamilton RL, Perez RG. Lewy-like aggregation of a-synuclein reduces protein phosphatase 2A activity in vitro and in vivo. Neuroscience. 2012; 207: 288-297
31. Grabowski GA. Phenotype, diagnosis, and treatment of Gaucher's disease. Lancet. 2008; 372: 1263-1271
32. Sidransky E, Nalls MA, Aasly JO, Aharon-Peretz J, Annesi G, Barbosa ER, Bar-Shira A, Berg D, Bras J, Brice A, Chen CM, Clark LN, Condroyer C, et al. Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease. N Engl J Med. 2009; 361: 1651-1661
33. Sidransky E, Lopez G. The link between the GBA gene and parkinsonism. Lancet Neurol. 2012; 11: 986-998
34. Mazzulli JR, Xu YH, Sun Y, Knight AL, McLean PJ, Caldwell GA, Sidransky E, Grabowski GA, Krainc D. Gaucher disease glucocerebrosidase and αsynuclein form a bidirectional pathogenic loop in synucleinopathies. Cell. 2011; 146: 37-52
35. Cooper AA, Gitler AD, Cashikar A, Haynes CM, Hill KJ, Bhullar B, Liu K, Xu K, Strathearn KE, Liu F, Cao S, Caldwell KA, Caldwell GA, et al. Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's models. Science. 2006; 313: 324-328
36. Thayanidhi N, Helm JR, Nycz DC, Bentley M, Liang Y, Hay JC. Alpha-synuclein delays endoplasmic reticulum (ER)-to-Golgi transport in mammalian cells by antagonizing ER/Golgi SNAREs. Mol Biol Cell. 2010; 21: 1850-1863
37. Galadari S, Hago A, Patel M. Effects of cations on ceramide-activated protein phosphatase 2A. Exp Mol Med. 2001; 33: 240-244
38. Murphy, KE, Gysbers AM, Abbott SK, Tayebi N, Kim WS, SidranskyE, Cooper A, Garner B, Halliday GM. Reduced glucocerebrosidase is associated with increased αsynuclein in sporadic Parkinson's disease. Brain. 2014; 137: 834-848
39. Braak H, Del Tredici, K Rüb U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging. 2003; 24:197-211
40. Yu S, Li X, Liu G, Han J, Zhang C, Li Y, Xu S, Liu C, Gao Y, Yang H, Uéda K, Chan P. Extensive nuclear localization of alpha-synuclein in normal rat brain neurons revealed by a novel monoclonal antibody. Neuroscience. 2007; 145: 539-555
41. Sasakawa H, Sakata E, Yamaguchi Y, Masuda M, Mori T, Kurimoto E, Iguchi T, Hisanaga S, Iwatsubo T, Hasegawa M, Kato K. Ultra-high field NMR studies of antibody binding and site-specific phosphorylation of-synuclein. Biochem Biophys Res Commun. 2007; 363: 795-799
42. Liu G, Chen M, Mi N, Yang W, Li X, Wang P, Yin N, Li Y, Yue F, Chan P, Yu S. Increased oligomerization and phosphorylation of αsynuclein are associated with decreased activity of glucocerebrosidase and protein phosphatase 2A in aging monkey brains. Neurobiol Aging. 2015; 36: 2649-2659
43. Qi Z, Yang W, Liu Y, Cui T, Gao H, Duan C, Lu L, Zhao C, Zhao H, Yang H. Loss of PINK1 function decreases PP2A activity and promotes autophagy in dopaminergic cells and a murine model. Neurochem Int. 2011; 59: 572-581
44. Alim MA, Hossain MS, Arima K, Takeda K, Izumiyama Y, Nakamura M, Kaji H, Shinoda T, Hisanaga S, Uéda K. Tubulin seeds alpha-synuclein fibril formation. J Biol Chem. 2002; 277: 2112-2117
45. Crawford GDJr, Le WD, Smith RG, Xie WJ, Stefani E, Appel SH. A novel N18TG29 mesencephalon cell hybrid expresses properties that suggest a dopaminergic cell line of substantia nigra origin. J Neurosci. 1992; 12: 3392-3398
46. Yu S, Zuo X, Li Y, Zhang C, Zhou M, Zhang YA, Uéda K, Chan P. Inhibition of tyrosine hydroxylase expression in alpha-synuclein-transfected dopaminergic neuronal cells. Neurosci Lett. 2004; 367: 34-39
47. Liao TT, Jia RW, Shi YL, Jia JW, Wang L, Chua H. Propidium iodide staining method for testing the cytotoxicity of 2, 4, 6-trichlorophenol and perfluorooctane sulfonate at low concentrations with Vero cells. J Environ Sci Health A Tox Hazard Subst Environ Eng. 2011; 46 (14): 1769-1775