Department of Chemistry, University of Kentucky, Lexington, KY 40506-0055, USA.
J Alzheimers Dis. 2013;33 Suppl 1:S243-51. doi: 10.3233/JAD-2012-129018.
Aging is the major risk factor associated with neurodegenerative diseases, including Alzheimer's disease (AD). Until now no clear understanding of the mechanisms of initiation and progression of this dementing disorder exists. Based on the studies that have been conducted so far amyloid β-peptide (Aβ), a protein found in senile plaques, one of the key pathological hallmarks of AD, has been reported to be critical in the pathogenesis of AD. Studies from our laboratory and others showed that Aβ can induce oxidative stress, which leads to oxidative modification of biomolecules, thereby diminishing the normal functions of neuronal cells and eventually leading to loss of neurons and AD. In this review paper, we summarize evidence of oxidative stress in brains of AD and mild cognitive impairment patients, as well as the results from redox proteomics studies. The investigations have provided insights into the downstream effects of oxidative modification of key brain proteins in the pathogenesis of AD. Based on these redox proteomics results, we suggest future areas of research that could be considered to better understand this devastating dementing disorder.
衰老是与神经退行性疾病相关的主要风险因素，包括阿尔茨海默病（AD）。到目前为止，人们对这种导致痴呆的疾病的起始和进展机制还没有明确的认识。基于迄今为止进行的研究，在老年斑中发现的一种蛋白质淀粉样β肽（Aβ）被认为是 AD 发病机制中的关键因素，淀粉样β肽是 AD 的关键病理特征之一。我们实验室和其他实验室的研究表明，Aβ 可诱导氧化应激，导致生物分子的氧化修饰，从而降低神经元细胞的正常功能，最终导致神经元丧失和 AD。在这篇综述论文中，我们总结了 AD 和轻度认知障碍患者大脑中氧化应激的证据，以及氧化还原蛋白质组学研究的结果。这些研究深入了解了 AD 发病机制中关键脑蛋白氧化修饰的下游效应。基于这些氧化还原蛋白质组学结果，我们建议考虑未来的研究领域，以更好地了解这种破坏性的痴呆症。
