阿尔茨海默病中三羧酸循环(TCA)循环的损伤:机制、意义和潜在的治疗方法。

IF 6.9 2区 医学 Q1 GERIATRICS & GERONTOLOGY
Gudimetla Susmitha Mohan, Rahul Kumar
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引用次数: 0

摘要

阿尔茨海默病(AD)是一种神经退行性疾病,以认知功能的逐渐损害、突触紊乱和广泛的神经元丧失为特征。新出现的证据表明,代谢损伤,特别是在三羧酸(TCA)循环中,在AD的病理生理中起着重要作用。TCA循环是代谢过程中不可缺少的途径,它负责能量的产生和细胞稳态的维持,特别是在神经元中。一些体外、临床和体内研究报告了几种TCA循环酶在AD期间被破坏。由于大脑的高代谢活动和持续的能量需求,TCA循环酶的破坏对大脑的影响更为明显,其中ATP产生的任何减少都会严重损害神经元功能,突触可塑性和整体认知过程。目前的综述探讨了AD相关的TCA循环损伤的机制,重点是TCA酶的分子改变。我们还讨论了TCA循环酶的潜在激活剂和抑制剂作为恢复AD相关代谢平衡的潜在治疗干预。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Impairment of Tricarboxylic Acid Cycle (TCA) Cycle in Alzheimer's Disease: Mechanisms, Implications, and Potential Therapies.

Alzheimer's disease (AD) is a neurodegenerative condition defined by the gradual impairment of cognitive functions, synaptic disarray, and extensive neuronal loss. Emerging evidence suggests that metabolic impairment, specifically within tricarboxylic acid (TCA) cycle, is instrumental in the AD pathophysiology. TCA cycle represents an indispensable pathway in metabolism that is responsible for energy production, and the maintenance of cellular homeostasis, particularly in neurons. Several in vitro, clinical, and in vivo studies reported that several TCA cycle enzymes disrupt during AD. Disruption in TCA cycle enzymes exhibits more pronounced impact on the brain owing to its high metabolic activity and continuous demand for energy, where any reduction in ATP production can severely impair neuronal function, synaptic plasticity, and overall cognitive processes. The current review explores the mechanisms underlying AD related impairment in TCA cycle, focussing on the molecular alterations of TCA enzymes. We also discussed potential activators and inhibitors of TCA cycle enzymes as a potential therapeutic intervention to restore AD related metabolic balance.

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来源期刊
Aging and Disease
Aging and Disease GERIATRICS & GERONTOLOGY-
CiteScore
14.60
自引率
2.70%
发文量
138
审稿时长
10 weeks
期刊介绍: Aging & Disease (A&D) is an open-access online journal dedicated to publishing groundbreaking research on the biology of aging, the pathophysiology of age-related diseases, and innovative therapies for conditions affecting the elderly. The scope encompasses various diseases such as Stroke, Alzheimer's disease, Parkinson’s disease, Epilepsy, Dementia, Depression, Cardiovascular Disease, Cancer, Arthritis, Cataract, Osteoporosis, Diabetes, and Hypertension. The journal welcomes studies involving animal models as well as human tissues or cells.
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