A Glimmer of Hope: Maintain Mitochondrial Homeostasis to Mitigate Alzheimer's Disease

Abstract

Mitochondria are classically known to be cellular energy producers. Given the high-energy demanding nature of neurons in the brain, it is essential that the mitochondrial pool remains healthy and provides a continuous and efficient supply of energy. However, mitochondrial dysfunction is inevitable in aging and neurodegenerative diseases. In Alzheimer's disease (AD), neurons experience unbalanced homeostasis like damaged mitochondrial biogenesis and defective mitophagy, with the latter promoting the disease-defining amyloid β (Aβ) and p-Tau pathologies impaired mitophagy contributes to inflammation and the aggregation of Aβ and p-Tau-containing neurotoxic proteins. Interventions that restore defective mitophagy may, therefore, alleviate AD symptoms, pointing out the possibility of a novel therapy. This review aims to illustrate mitochondrial biology with a focus on mitophagy and propose strategies to treat AD while maintaining mitochondrial homeostasis.

Keywords: Alzheimer’s disease; NAD+; mitochondria dysfunction; mitophagy.

Figure 1.

Mitochondrial cell biology. (A) structure of mitochondrion and general features of mitochondrial dynamics (B) fusion (C) fission.

Figure 2.

Overview of autophagy/mitophagy in neurons.