A review of mitochondrial dysfunction, pathophysiology and therapeutic prospects in neurodegenerative diseases

Abstract

Mitochondria plays a fundamental role in maintaining neural health because neurons have significant energy requirements. They sustain Ca 2+ homeostasis and supply vital energy, both of which are necessary for healthy neuronal development and function. In recent years, mitochondrial dysfunction and obstructed mitochondrial dynamics has become a pathological characteristic of several neurodegenerative disorders. Some of the neurodegenerative diseases that are affected by mitochondrial damage include Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and Amyotrophic Lateral Sclerosis (ALS), which have been associated with certain protein build-ups and anatomic susceptibility. Numerous mechanisms of interaction between neurodegeneration and mitochondrial injury have been proposed. From genetic mutations and environmental disturbances to increased oxidative stress which is caused by reactive oxygen species (ROS), as well as changes in non-cell autonomous mechanisms and other cellular systems (such as protein homeostasis, DNA/RNA repair and metabolism, nucleocytoplasmic and vesicular transport, etc.). Furthermore, compromised electron transport chain function and disturbed quality-control processes, including mitophagy, during the early stages of disease development and chronic neuro-inflammation might create feedback loops that intensify neuronal degeneration. In this narrative review, we explore the specific mitochondrial disruptive mechanisms that are involved in each of the mentioned neurodegenerative diseases, their pathophysiology, emerging therapeutic strategies, and limitations as well as the proposed interventions for future research.