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| 001 | 281812 | ||
| 005 | 20251112132214.0 | ||
| 024 | 7 | _ | |a 10.1038/s41531-025-01159-w |2 doi |
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| 037 | _ | _ | |a DZNE-2025-01195 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Vasili, Eftychia |b 0 |
| 245 | _ | _ | |a Glycation of alpha-synuclein enhances aggregation and neuroinflammatory responses. |
| 260 | _ | _ | |a [London] |c 2025 |b Springer Nature |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1762949811_29014 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a The risk of developing Parkinson's disease (PD) is elevated in individuals with type 2 diabetes (T2DM), but the molecular pathways underlying this link remain unclear. Glycation, a non-enzymatic modification of lysine and arginine residues by reducing sugars or reactive dicarbonyls, may disrupt proteostasis and trigger pathology. Here, we investigated how methylglyoxal (MGO)- and ribose-mediated glycation influence aSyn aggregation, neuroinflammation, and detoxification pathways. Using SH-SY5Y cells, primary neurons, primary microglia and MGO-injected aSyn transgenic mice, we found that MGO-glycated aSyn promotes PD associated pathological features, including pS129-positive aSyn aggregates, neuroinflammation, and impairment of the glyoxalase detoxification pathway. Ribose-glycated aSyn, while immunogenic, exerts limited effects on aggregation and seeding. Both glycated species activates microglia and upregulate pro-inflammatory markers. We further developed a novel antibody specific for MGO-glycated aSyn, which selectively detects Lewy body-like deposits in dementia with Lewy bodies (DLB) tissue and MGO-injected mice. These findings implicate MGO-glycation in PD-T2DM comorbidity. |
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| 700 | 1 | _ | |a König, Annekatrin |b 1 |
| 700 | 1 | _ | |a Al-Azzani, Mohammed |b 2 |
| 700 | 1 | _ | |a Bosbach, Clara |b 3 |
| 700 | 1 | _ | |a Gatzemeier, Luisa Maria |b 4 |
| 700 | 1 | _ | |a Thom, Searlait |b 5 |
| 700 | 1 | _ | |a Chegão, Ana |b 6 |
| 700 | 1 | _ | |a Miranda, Hugo Vicente |b 7 |
| 700 | 1 | _ | |a Steinem, Claudia |b 8 |
| 700 | 1 | _ | |a Erskine, Daniel |b 9 |
| 700 | 1 | _ | |a Outeiro, Tiago F |0 P:(DE-2719)2814138 |b 10 |e Last author |u dzne |
| 773 | _ | _ | |a 10.1038/s41531-025-01159-w |g Vol. 11, no. 1, p. 307 |0 PERI:(DE-600)2819218-7 |n 1 |p 307 |t npj Parkinson's Disease |v 11 |y 2025 |x 2373-8057 |
| 856 | 4 | _ | |u https://pub.dzne.de/record/281812/files/DZNE-2025-01195%20SUP.pdf |
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| 910 | 1 | _ | |a Deutsches Zentrum für Neurodegenerative Erkrankungen |0 I:(DE-588)1065079516 |k DZNE |b 10 |6 P:(DE-2719)2814138 |
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