Mitochondrial Dysfunction and Biogenesis in Neurodegenerative diseases: Pathogenesis and Treatment

Abstract

Neurodegenerative diseases are a heterogeneous group of disorders that are incurable and characterized by the progressive degeneration of the function and structure of the central nervous system (CNS) for reasons that are not yet understood. Neurodegeneration is the umbrella term for the progressive death of nerve cells and loss of brain tissue. Because of their high energy requirements, neurons are especially vulnerable to injury and death from dysfunctional mitochondria. Widespread damage to mitochondria causes cells to die because they can no longer produce enough energy. Several lines of pathological and physiological evidence reveal that impaired mitochondrial function and dynamics play crucial roles in aging and pathogenesis of neurodegenerative diseases. As mitochondria are the major intracellular organelles that regulate both cell survival and death, they are highly considered as a potential target for pharmacological-based therapies. The purpose of this review was to present the current status of our knowledge and understanding of the involvement of mitochondrial dysfunction in pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) and the importance of mitochondrial biogenesis as a potential novel therapeutic target for their treatment. Likewise, we highlight a concise overview of the key roles of mitochondrial electron transport chain (ETC.) complexes as well as mitochondrial biogenesis regulators regarding those diseases.

Keywords: Mitochondrial Biogenesis; Mitochondrial Dysfunction; Mitochondrial complexes; Neurodegenerative Diseases; Pathogenesis; Treatment.

Figure 1

Regulation of mitochondrial quality control by fission and fusion phenomena.

Figure 2

Mitochondrial complex defects in pathogenesis of AD, PD, HD, and ALS.

Figure 3

Mitochondrial biogenesis as a novel therapeutic target in treatment of AD, PD, HD, and ALS.

Figure 4

Limitation of the pathological progression, neurodegeneration, and cell death in AD through increasing the PGC‐1α activity as a key regulator of the mitochondrial biogenesis.

Figure 5

Limitation of the pathological progression, neurodegeneration, and cell death in PD through increasing the PGC‐1α activity as a key regulator of the mitochondrial biogenesis.

Figure 6

Limitation of the pathological progression, neurodegeneration, and cell death in HD through increasing the PGC‐1α activity as a key regulator of the mitochondrial biogenesis.

Figure 7

Limitation of the pathological progression, neurodegeneration, and cell death in ALS through increasing the PGC‐1α activity as a key regulator of the mitochondrial biogenesis.