PMC

Summary scheme of glucose toxicity and the documented anomalies in SNCA-KO brain. This schematic depicts the consequences of glucose-induced damage with generation of reactive carbonyls, advanced glycation endproducts and exemplary protein aggregation disorders, a process mitigated by the induction of the cytoprotective glyoxalase system which exerts an anti-AGE effect and modulates the disease risk. Black arrows illustrate the changes observed in SNCA-KO brains

Elevated GLO1 activity and dicarbonyl stress in alpha-synuclein-deficient mouse brain. Brainstem/midbrain and cortex from old WT and KO mice were analyzed for GLO1 enzymatic activity (a, b) and dicarbonyl stress markers glyoxal (c, d), methylglyoxal (e, f) and the non-GLO1 dependent dicarbonyl 3-DG (g, h). Data are presented as mean ± SD and significant differences were highlighted with asterisks (*p < 0.05 and ***p < 0.001; t test). n = 6 animals/genotype

Elevation of GLO1 protein levels in striatum of alpha-synuclein-deficient mice. a Immunoblot analysis revealed b significant elevated GLO1 protein levels (3.26 ± 0.32-fold; n = 5/genotype, p = 0.0003) in the striatum of KO mice at old age (19 months) in comparison with corresponding WT controls. Protein expression levels of beta-actin were used for normalization of GLO1 protein levels and to confirm equal protein loading. Data are presented as mean ± SD and significant differences were highlighted with asterisks (***p < 0.001; t test). n = 5 animals/genotype

Reduced exploratory motor activity in alpha-synuclein-deficient mice. Automatic recording of the spontaneous movement of untrained old mice over 5 min by infrared beams and calculating the time spent within the 5 × 5 cm chamber center versus the margins showed a significant preference of KO animals to spend time in the “protected” environment close to the walls (n = 22 WT vs. n = 28 KO). Data are presented as mean ± SD and significant differences were highlighted with asterisks (*p < 0.05; t test)