Ibrahim Abdallah Mohammad, Pottoo Faheem Hyder, Dahiya Ekta Singh, Khan Firdos Alam, Kumar J B Senthil
Fundamentals of Nursing Department, College of Nursing, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
Eur J Neurosci. 2020 Jul;52(2):2931-2943. doi: 10.1111/ejn.14838. Epub 2020 Jun 28.
Neurodegenerative disorders present with progressive and irreversible degeneration of the neurons. Alzheimer's disease (AD) is one of the most common neurodegenerative disorders affecting 50 million people worldwide (2017), expected to be doubled every 20 years. Primarily affected by age, AD is the cause for old-age dementia, progressive memory loss, dysfunctional thoughts, confusion, cognitive impairment and personality changes. Neuroglia formerly understood as "glue" of the brain neurons consists of macroglia (astrocytes and oligodendrocyte), microglia and progenitors NG2-glia, and constitute a large fraction of the mammalian brain. The primary functions of glial cells are to provide neurons with metabolic and structural support in the healthy brain; however, they attain a "reactive" state from the "resting" state upon challenged with a pathological insult such as a neurodegenerative cascade. Failure or defects in their homoeostatic functions (i.e. concentration of ions, neurotransmitters) ultimately jeopardize neurons with excitotoxicity and oxidative stress. Moreover, the most common clinical outcome of AD is the cognitive impairment and memory loss, which are attributed mainly by the accumulation of Aβ. Failure of glial cells to remove the Aβ toxic proteins accelerates the AD progression. The rapidly emerging proteomic techniques such as mass spectrometry (MS), cross-linking mass spectrometry, hydrogen deuterium trade mass spectrometry, protein foot printing and 2-DGE combined with LC-MS/MS present wide array of possibilities for the identification of differentially expressed proteins in AD.
神经退行性疾病表现为神经元的进行性和不可逆性退化。阿尔茨海默病（AD）是最常见的神经退行性疾病之一，2017年全球有5000万人受其影响，预计每20年增加一倍。AD主要受年龄影响，是老年痴呆、进行性记忆丧失、思维功能障碍、意识混乱、认知障碍和人格改变的病因。神经胶质细胞以前被认为是脑神经元的“胶水”，由大胶质细胞（星形胶质细胞和少突胶质细胞）、小胶质细胞和祖细胞NG2-胶质细胞组成，在哺乳动物大脑中占很大比例。胶质细胞的主要功能是在健康大脑中为神经元提供代谢和结构支持；然而，当受到诸如神经退行性级联反应等病理损伤挑战时，它们会从“静止”状态转变为“反应性”状态。其稳态功能（即离子、神经递质的浓度）的失败或缺陷最终会因兴奋性毒性和氧化应激而危及神经元。此外，AD最常见的临床结果是认知障碍和记忆丧失，这主要归因于β淀粉样蛋白（Aβ）的积累。胶质细胞无法清除Aβ毒性蛋白会加速AD的进展。快速兴起的蛋白质组学技术，如质谱（MS）、交联质谱、氢氘交换质谱、蛋白质足迹法和二维凝胶电泳结合液相色谱-串联质谱，为鉴定AD中差异表达的蛋白质提供了广泛的可能性。
