Affiliations: [a]
Yuebei People’s Hospital, Affiliated Hospital of Shantou University Medical College, Shaoguan, Guangdong Province, China
| [b]
Department of Gerontology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, China
| [c]
Department of Blood Transfusion, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, China
Correspondence:
[*]
Correspondence to: Huiyi Chen, No. 133 Huimin South Road, Wujiang District, Shaoguan, Guangdong Province, 512000, China. Tel.: +86 13650359575; E-mail: [email protected] and Yanfang He, No. 57 Ren min da dao Road Nan, Xiashan District, Zhanjiang, Guangdong Province, 524001, China. Tel.: +86 13420193560; E-mail: [email protected].
Abstract: Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders and is characterized by a decrease in learning capacity, memory loss and behavioral changes. In addition to the well-recognized amyloid-β cascade hypothesis and hyperphosphorylated Tau hypothesis, accumulating evidence has led to the proposal of the mitochondrial dysfunction hypothesis as the primary etiology of AD. However, the predominant molecular mechanisms underlying the development and progression of AD have not been fully elucidated. Mitochondrial dysfunction is not only considered an early event in AD pathogenesis but is also involved in the whole course of the disease, with numerous pathophysiological processes, including disordered energy metabolism, Ca2+ homeostasis dysfunction and hyperactive oxidative stress. In the current review, we have integrated emerging evidence to summarize the main mitochondrial alterations— bioenergetic metabolism, mitochondrial inheritance, mitobiogenesis, fission– fusion dynamics, mitochondrial degradation, and mitochondrial movement— underlying AD pathogenesis; precisely identified the mitochondrial regulators; discussed the potential mechanisms and primary processes; highlighted the leading players; and noted additional incidental signaling pathway changes. This review may help to stimulate research exploring mitochondrial metabolically-oriented neuroprotection strategies in AD therapies, leading to a better understanding of the link between the mitochondrial dysfunction hypothesis and AD pathogenesis.
