TY  - JOUR
AU  - Vasili, Eftychia
AU  - König, Annekatrin
AU  - Al-Azzani, Mohammed
AU  - Bosbach, Clara
AU  - Gatzemeier, Luisa Maria
AU  - Thom, Searlait
AU  - Chegão, Ana
AU  - Miranda, Hugo Vicente
AU  - Steinem, Claudia
AU  - Erskine, Daniel
AU  - Outeiro, Tiago F
TI  - Glycation of alpha-synuclein enhances aggregation and neuroinflammatory responses.
JO  - npj Parkinson's Disease
VL  - 11
IS  - 1
SN  - 2373-8057
CY  - [London]
PB  - Springer Nature
M1  - DZNE-2025-01195
SP  - 307
PY  - 2025
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:41131060
DO  - DOI:10.1038/s41531-025-01159-w
UR  - https://pub.dzne.de/record/281812
ER  -