Site-specific mitochondrial dysfunction in neurodegeneration

Abstract

Mitochondria are essential for neuronal survival and mitochondrial dysfunction is a hallmark of neurodegeneration. The loss in mitochondrial energy production, oxidative stress, and changes in calcium handling are associated with neurodegenerative diseases; however, different sites and types of mitochondrial dysfunction are linked to distinct neuropathologies. Understanding the causal or correlative relationship between changes in mitochondria and neuropathology will lead to new therapeutic strategies. Here, we summarize the evidence of site-specific mitochondrial dysfunction and mitochondrial-related clinical trials for neurodegenerative diseases. We further discuss potential therapeutic approaches, such as mitochondrial transplantation, restoration of mitochondrial function, and pharmacological alleviation of mitochondrial dysfunction.

Keywords: Mitochondria-targeting therapeutics; Mitochondrial dysfunction; Neurodegeneration; Optogenetics; Transplantation.