Mitochondria-targeting by small molecules against Alzheimer's disease: A mechanistic perspective

Abstract

Alzheimer's disease (AD) poses a considerable worldwide health obstacle, marked by gradual cognitive deterioration and neuronal loss. While the molecular mechanisms underlying AD pathology have been elucidated to some extent, therapeutic options remain limited. Mitochondrial dysfunction has become recognized as a significant factor in the development of AD, with oxidative stress and disrupted energy metabolism being critical elements. This review explores the mechanistic aspects of small molecule targeting of mitochondria as a potential therapeutic approach for AD. The review explores the role of mitochondrial dysfunction in AD, including its involvement in the accumulation of β-amyloid plaques and neurofibrillary tangles, synaptic dysfunction, and neuronal death. Furthermore, the effects of oxidative stress on mitochondrial function were investigated, including the resulting damage to mitochondrial components. Mitochondrial-targeted therapies have attracted attention for their potential to restore mitochondrial function and reduce AD pathology. The review outlines the latest preclinical and clinical evidence supporting the effectiveness of small molecules in targeting mitochondrial dysfunction in AD. Additionally, it discusses the molecular pathways involved in mitochondrial dysfunction and examines how small molecules can intervene to address these abnormalities. By providing a comprehensive overview of the latest research in this field, this review aims to shed light on the therapeutic potential of small molecule targeting of mitochondria in AD and stimulate further research in this promising area of drug development.