Mainali Nirjal, Ayyadevara Srinivas, Ganne Akshatha, Shmookler Reis Robert J, Mehta Jawahar L
Bioinformatics Program, University of Arkansas at Little Rock and University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Department of Geriatrics and Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
J Cardiovasc Aging. 2023;3(2). doi: 10.20517/jca.2023.4. Epub 2023 Mar 7.
Protein homeostasis, the balance between protein synthesis and degradation, requires the clearance of misfolded and aggregated proteins and is therefore considered to be an essential aspect of establishing a physiologically effective proteome. Aging alters this balance, termed "proteostasis", resulting in the progressive accumulation of misfolded and aggregated proteins. Defective proteostasis leads to the functional deterioration of diverse regulatory processes during aging and is implicated in the etiology of multiple pathological conditions underlying a variety of neurodegenerative diseases and in age-dependent cardiovascular disease. Detergent-insoluble protein aggregates have been reported by us in both aged and hypertensive hearts. The protein constituents were found to overlap with protein aggregates seen in neurodegenerative diseases such as Alzheimer's disease. Therefore, targeting these protein components of aggregates may be a promising therapeutic strategy for cardiovascular pathologies associated with aging, ischemia, and/or hypertension.
蛋白质稳态，即蛋白质合成与降解之间的平衡，需要清除错误折叠和聚集的蛋白质，因此被认为是建立生理有效蛋白质组的一个重要方面。衰老会改变这种被称为“蛋白质稳态”的平衡，导致错误折叠和聚集蛋白质的逐渐积累。蛋白质稳态缺陷会导致衰老过程中各种调节过程的功能恶化，并与多种神经退行性疾病以及年龄依赖性心血管疾病的多种病理状况的病因有关。我们在老年心脏和高血压心脏中均发现了去污剂不溶性蛋白质聚集体。这些蛋白质成分被发现与在诸如阿尔茨海默病等神经退行性疾病中所见的蛋白质聚集体重叠。因此，针对这些聚集体的蛋白质成分可能是治疗与衰老、缺血和/或高血压相关的心血管疾病的一种有前景的治疗策略。
