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The Role of Mitophagy in Various Neurological Diseases as a Therapeutic Approach

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Abstract

Mitochondria are critical to multiple cellular processes, from the production of adenosine triphosphate (ATP), maintenance of calcium homeostasis, synthesis of key metabolites, and production of reactive oxygen species (ROS) to maintain necrosis, apoptosis, and autophagy. Therefore, proper clearance and regulation are essential to maintain various physiological processes carried out by the cellular mechanism, including mitophagy and autophagy, by breaking down the damaged intracellular connections under the influence of various genes and proteins and protecting against various neurodegenerative diseases such as Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), Alzheimer disease (AD), and Huntington disease (HD). In this review, we will discuss the role of autophagy, selective macroautophagy, or mitophagy, and its role in neurodegenerative diseases along with normal physiology. In addition, this review will provide a better understanding of the pathways involved in neuron autophagy and mitophagy and how mutations affect these pathways in the various genes involved in neurodegenerative diseases. Various new findings indicate that the pathways that remove dysfunctional mitochondria are impaired in these diseases, leading to the deposition of damaged mitochondria. Apart from that, we have also discussed the therapeutic strategies targeting autophagy and mitophagy in neurodegenerative diseases.

Graphical Abstract

The mitophagy cycle results in the degradation of damaged mitochondria and the biogenesis of new healthy mitochondria, also highlighting different stages at which a particular neurodegenerative disease could occur

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Abbreviations

AD:

Alzheimer's disease

ALS:

Amyotrophic lateral sclerosis

APP:

Amyloid precursor protein

ATP:

Adenosine triphosphate

BDNF:

Brain-derived neurotrophic factor

DCT-1:

(DAF-16/FOXO-controlled germline-tumor-affecting-1)-dependent pathway

CMA:

Chaperone-mediated autophagy

HD:

Huntington’s disease

HTT:

Huntington

IMM:

Inner mitochondrial membrane

LB:

Lewy bodies

LN:

Lewy Neuritis

mtDNA:

Mitochondrial DNA

Mfn1 and Mfn2:

Mitofusin 1 and 2

MND:

Motor neuron disease

MPAT:

Microtubule-linked protein Tau

MUL1:

Mitochondrial ubiquitin ligase 1

OMM:

Outer mitochondrial membrane

OPA1:

Optic dominant atrophy 1

OPTN:

Optineurin

OXPHOS:

Oxidative phosphorylation

PD:

Parkinson's disease

PINK1:

PTEN-induced kinase1

PDR-1:

Parkinson disease-related-1; parkin

ROS:

Reactive oxygen species

SREBF1:

Sterol regulatory element-binding transcription factor1

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Acknowledgements

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Authors and Affiliations

  1. Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, 142001, India

    Simranjit Kaur, Neelam Sharma, Vishal Kumar, Deepali Sharma, Bhawna Devi, Lakshay Kapil & Arti Singh

  2. Department of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab, 142001, India

    Charan Singh

  3. IK Gujral Punjab Technical University, Jalandhar, Punjab, India

    Simranjit Kaur, Neelam Sharma, Vishal Kumar, Deepali Sharma, Bhawna Devi, Lakshay Kapil, Charan Singh & Arti Singh

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SK and NS conducted the literature search and drafted the manuscript. SK prepares the illustration for the manuscript. VK and CS helped revise the manuscript. AS conceived the original idea and designed the outline of the study. All authors read and approved the final manuscript.

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Kaur, S., Sharma, N., Kumar, V. et al. The Role of Mitophagy in Various Neurological Diseases as a Therapeutic Approach. Cell Mol Neurobiol 43, 1849–1865 (2023). https://doi.org/10.1007/s10571-022-01302-8

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