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帕金森病和阿尔茨海默病中的糖基化作用。

Glycation in Parkinson's disease and Alzheimer's disease.

作者信息

Vicente Miranda Hugo, El-Agnaf Omar M A, Outeiro Tiago Fleming

机构信息

CEDOC - Chronic Diseases Research Center, NOVA Medical School, Lisboa, Portugal.

Neurological Disorders Center, Qatar Biomedical Research Institute, and College of Science and Engineering, Hamad Bin Khalifa University (HBKU), Education City, Qatar Foundation, P.O. Box 5825 Doha, Qatar.

出版信息

Mov Disord. 2016 Jun;31(6):782-90. doi: 10.1002/mds.26566. Epub 2016 Mar 4.

Abstract

Glycation is a spontaneous age-dependent posttranslational modification that can impact the structure and function of several proteins. Interestingly, glycation can be detected at the periphery of Lewy bodies in the brain in Parkinson's disease. Moreover, α-synuclein can be glycated, at least under experimental conditions. In Alzheimer's disease, glycation of amyloid β peptide exacerbates its toxicity and contributes to neurodegeneration. Recent studies establish diabetes mellitus as a risk factor for several neurodegenerative disorders, including Parkinson's and Alzheimer's diseases. However, the mechanisms underlying this connection remain unclear. We hypothesize that hyperglycemia might play an important role in the development of these disorders, possibly by also inducing protein glycation and thereby dysfunction, aggregation, and deposition. Here, we explore protein glycation as a common player in Parkinson's and Alzheimer's diseases and propose it may constitute a novel target for the development of strategies for neuroprotective therapeutic interventions. © 2016 International Parkinson and Movement Disorder Society.

摘要

糖基化是一种随年龄增长而自发发生的翻译后修饰,可影响多种蛋白质的结构和功能。有趣的是,在帕金森病患者大脑的路易小体周围可检测到糖基化。此外,至少在实验条件下,α-突触核蛋白可发生糖基化。在阿尔茨海默病中,淀粉样β肽的糖基化会加剧其毒性并导致神经退行性变。最近的研究表明,糖尿病是包括帕金森病和阿尔茨海默病在内的几种神经退行性疾病的危险因素。然而,这种关联背后的机制仍不清楚。我们推测,高血糖可能在这些疾病的发展中起重要作用,可能也是通过诱导蛋白质糖基化,从而导致功能障碍、聚集和沉积。在此,我们探讨蛋白质糖基化在帕金森病和阿尔茨海默病中作为一个共同因素的作用,并提出它可能构成神经保护治疗干预策略开发的一个新靶点。© 2016国际帕金森病和运动障碍协会。

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