Physical Activity Alleviates Cognitive Dysfunction of Alzheimer's Disease through Regulating the mTOR Signaling Pathway

Abstract

Alzheimer's disease (AD) is one of the most common aging-related progressive neurodegenerative disorders, and can result in great suffering for a large portion of the aged population. Although the pathogenesis of AD is being elucidated, the exact mechanisms are still unclear, thereby impeding the development of effective drugs, supplements, and other interventional strategies for AD. In recent years, impaired autophagy associated with microRNA (miRNA) dysfunction has been reported to be involved in aging and aging-related neurodegenerative diseases. Therefore, miRNA-mediated regulation for the functional status of autophagy may become one of the potent interventional strategies for AD. Mounting evidence from in vivo AD models has demonstrated that physical activity can exert a neuroprotective role in AD. In addition, autophagy is strictly regulated by the mTOR signaling pathway. In this article, the regulation of the functional status of autophagy through the mTOR signaling pathway during physical activity is systematically discussed for the prevention and treatment of AD. This concept will be beneficial to developing novel and effective targets that can create a direct link between pharmacological intervention and AD in the future.

Keywords: Alzheimer’s disease; autophagy; mTOR signal pathway; microRNA; physical activity.

Figure 1

Physical activity as an mTOR suppressor can alleviate cognitive dysfunction and rescue abnormal miRNAs in AD for regulating functional status of autophagy, tau hyperphosphorylation, and the accumulation of Aβ and NFTs, thus accomplishing the mitigation of AD. Meanwhile, mTOR could be considered as the preventive and therapeutic target to develop novel and effective intervention strategies for AD and other neurodegenerative diseases. The solid arrows present the activation and the dotted arrows present the suppression, as well as question symbols presents the uncertainty.