Molecular Physiology and Biophysics Unit, Department of Biology, University of Padova, Padova, Italy.
Department of Experimental Neurodegeneration, University Medical Center Goettingen, Goettingen, Germany.
Mol Neurobiol. 2018 Nov;55(11):8754-8763. doi: 10.1007/s12035-018-1025-9. Epub 2018 Mar 28.
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.
2 型糖尿病（T2DM）是一种代谢紊乱，其特征是血液中葡萄糖浓度升高。慢性高血糖状态是与该疾病相关的大多数血管并发症的主要原因，而目前流行的机制与甲基乙二醛（MG）介导的糖化化学有关，MG 在 T2DM 中积累。近年来，人们明显发现 2 型糖尿病患者患帕金森病（PD）的风险更高，但 T2DM 和 PD 之间相互作用的分子机制仍不清楚。多巴胺的氧化化学及其与蛋白质α-突触核蛋白（aS）的反应性与 PD 的发病机制有关。最近，aS 也被描述为与 MG 相互作用。有趣的是，MG 和多巴胺氧化产物既有结构相似性又有化学反应性。MG 扩散到其产生部位并与 aS 反应的能力可以解释 T2DM 患者 PD 发病率较高的原因，并可能为开发新的策略来拮抗 PD 的发生提供机会。
