Physiological Roles of Hippo Signaling Pathway and Autophagy in Dementia

Abstract

Background: Dementia is a neurocognitive disorder associated with the aging brain and mainly affects the hippocampus and cerebral cortex. The Hippo signaling pathway and autophagy proteins have been found to be perturbed in the brain affected by dementia processes.

Objective: This systematic review aims to elaborate on the involvement of the Hippo signaling pathway and autophagy in modulating the progression and severity of dementia in aging.

Methods: Searches were conducted on MEDLINE, Google Scholar, Scopus, and Web of Science databases.

Results: The Hippo signaling pathway is dependent upon the transcriptional co-activator YAP/TAZ, which forms complexes with TEAD in the nucleus in order to maintain cell homeostasis. When the expression YAP/TAZ is reduced, transcriptional repression-induced atypical cell death, ballooning cell death, and necrosis will consequently occur in the neurons. Moreover, the autophagic proteins, such as LC3, ATG proteins, and Beclin, are reduced, resulting in the disruption of autophagosome formation and accumulation and the spread of misfolded proteins in the brain suffering from dementia.

Conclusion: The impairment of the Hippo signaling pathway and autophagy in the dementia process in aging should be considered since it might predict the severity, treatment, and prevention of dementia.

Keywords: Aging; Hippo signaling pathway; autophagy; brain; dementia; neurodegeneration.