Mitochondrial mechanisms in Alzheimer?s disease: Quest for therapeutics

Mitochondrial function is essential for maintaining neuronal integrity, because neurons have a high energy demand. Neurodegenerative diseases, such as Alzheimer's disease (AD), are exacerbated by mitochondrial dysfunction. Mitochondrial autophagy (mitophagy) attenuates neurodegenerative diseases by eradicating dysfunctional mitochondria. In neurodegenerative disorders, there is disrup-tion of the mitophagy process. High levels of iron also interfere with the mitophagy process and the mtDNA released after mitophagy is proinflammatory and triggers the cGAS-STING pathway that aids AD pathology. In this review, we critically discuss the factors that affect mitochondrial impairment and different mitophagy processes in AD. Furthermore, we discuss the molecules used in mouse studies as well as clinical trials that could result in potential therapeutics in the future.

Automated summary

Mitochondrial function is crucial for neuronal health due to their high energy demand. Dysfunction in mitochondria exacerbates neurodegenerative diseases like Alzheimer's disease. Mitophagy, the process of eliminating dysfunctional mitochondria, plays a protective role in attenuating neurodegenerative disorders. However, disruptions in the mitophagy process and the release of proinflammatory mtDNA can contribute to AD pathology. This review critically examines the factors influencing mitochondrial impairment and different mitophagy processes in AD, as well as potential therapeutic molecules studied in mouse models and clinical trials.