The Role of Mitochondrial Dysfunction in Alzheimer’s: Molecular Defects and Mitophagy-Enhancing Approaches

Abstract

Alzheimer’s disease (AD), a progressive and chronic neurodegenerative syndrome, is categorized by cognitive and memory damage caused by the aggregations of abnormal proteins, specifically including Tau proteins and β-amyloid in brain tissue. Moreover, mitochondrial dysfunctions are the principal causes of AD, which is associated with mitophagy impairment. Investigations exploring pharmacological therapies alongside AD have explicitly concentrated on molecules accomplished in preventing/abolishing the gatherings of the abovementioned proteins and mitochondria damages. Mitophagy is the removal of dead mitochondria by the autophagy process. Damages in mitophagy, the manner of diversified mitochondrial degeneracy by autophagy resulting in an ongoing aggregation of malfunctioning mitochondria, were also suggested to support AD. Recently, plentiful reports have suggested a link between defective mitophagy and AD. This treaty highlights updated outlines of modern innovations and developments on mitophagy machinery dysfunctions in AD brains. Moreover, therapeutic and nanotherapeutic strategies targeting mitochondrial dysfunction are also presented in this review. Based on the significant role of diminished mitophagy in AD, we suggest that the application of different therapeutic approaches aimed at stimulating mitophagy in AD would be beneficial for targeting or reducing the mitochondrial dysfunction induced by AD.