Autophagy of Mitochondria: A Promising Therapeutic Target for Neurodegenerative Disease

Abstract

The autophagic process is the only known mechanism for mitochondrial turnover and it has been speculated that dysfunction of autophagy may result in mitochondrial error and cellular stress. Emerging investigations have provided new understanding of how autophagy of mitochondria (also known as mitophagy) is associated with cellular oxidative stress and its impact on neuro-degeneration. This impaired autophagic function may be considered as a possible mechanism in the pathogenesis of several neurodegenerative disorders including: Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Huntington disease (HD). It can be suggested that autophagy dysfunction along with oxidative stress are considered main events in neurodegenerative disorders. New therapeutic approaches have now begun to target mitochondria as a potential drug target. This review discusses evidence supporting the notion that oxidative stress and autophagy are intimately associated with neurodegenerative disease pathogenesis. This review also explores new approaches that can prevent mitochondrial dysfunction, improve neurodegenerative etiology, and also offer possible cures to the aforementioned neurodegenerative diseases.

Autophagic flux induced by graphene oxide has a neuroprotective effect against human prion protein fragments

“…40 Maintenance of mitochondrial homeostasis and protection against oxidative stress may be the main therapeutic strategy for prevention of progression in neurodegenerative diseases, including Alzheimer's and prion disease. [41][42][43] Recent studies have suggested that the activating autophagic flux prevents prion-mediated neurotoxicity via protection of mitochondrial function and prevention of oxidative stress. decreased by GO treatment.…”

Novel Approaches of Oxidative Stress Mechanisms in the Multiple Sclerosis Pathophysiology and Therapy

“…Hydralazine may become a potential therapy due to the fact that it protects cells from the damaging effects of acrolein (61,83,84). The following agents could offer help in preventing mitochondrial dysfunction and in improving neurodegeneration: CDDO-ethyl amide, CDDO-trifluoroethylamide, pioglitazone, rosiglitazone, resveratrol, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), and bezafibrate (85).…”

Mitophagy and the therapeutic clearance of damaged mitochondria for neuroprotection

“…Parkinson disease (PD) is characterised by the loss of neurons in the substantia nigra and the formation of intra-neuronal α-synuclein aggregates (Kamat et al, 2014). Mutations in the PINK1 and Parkin genes are well known causes of autosomal recessive forms of PD, and numerous studies (Pickrell and Youle, 2015) link this to the role of these gene products in mitochondrial quality control (Figure 2).…”

“…Mitochondrial homeostasis is a delicate balancing-act: too few mitochondria will result in low ATP levels and bioenergetics failure, whereas too many can generate detrimental levels of ROS and leak CytC. Consequently, maintenance of a healthy mitochondrial population is essential for cellular function and survival, and mitochondrial dysfunction has been implicated in a variety of neurological pathologies (Kamat et al, 2014).…”