Mitochondria and Brain Disease: A Comprehensive Review of Pathological Mechanisms and Therapeutic Opportunities

Abstract

Mitochondria play a vital role in maintaining cellular energy homeostasis, regulating apoptosis, and controlling redox signaling. Dysfunction of mitochondria has been implicated in the pathogenesis of various brain diseases, including neurodegenerative disorders, stroke, and psychiatric illnesses. This review paper provides a comprehensive overview of the intricate relationship between mitochondria and brain disease, focusing on the underlying pathological mechanisms and exploring potential therapeutic opportunities. The review covers key topics such as mitochondrial DNA mutations, impaired oxidative phosphorylation, mitochondrial dynamics, calcium dysregulation, and reactive oxygen species generation in the context of brain disease. Additionally, it discusses emerging strategies targeting mitochondrial dysfunction, including mitochondrial protective agents, metabolic modulators, and gene therapy approaches. By critically analysing the existing literature and recent advancements, this review aims to enhance our understanding of the multifaceted role of mitochondria in brain disease and shed light on novel therapeutic interventions.

Keywords: brain disease; mitochondria; mitochondrial DNA mutations; mitochondrial dynamics; mitochondrial protective agents; neurodegenerative disorders; oxidative phosphorylation; reactive oxygen species.

Figure 1

Consequences of mitochondrial dysfunction depending on glia cells or neuron types [37,62,63].

Figure 2

Mitochondrial dysfunction in biogenesis processes and dynamics triggers neurodegenerative diseases.

Figure 3

Brain diseases brought on by inflammation and resulting from mitochondrial malfunction.