Targeting mitophagy for neurological disorders treatment: advances in drugs and non-drug approaches

Mitochondria serve as a vital energy source for nerve cells. The mitochondrial network also acts as a defense mechanism against external stressors that can threaten the stability of the nervous system. However, excessive accumulation of damaged mitochondria can lead to neuronal death. Mitophagy is a...

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Bibliographic Details
Published in:Naunyn-Schmiedeberg's archives of pharmacology 2023-12, Vol.396 (12), p.3503-3528
Main Authors: Yang, Xiong, Zhang, Yu, Luo, Jia-xin, Zhu, Tao, Ran, Zhao, Mu, Ben-Rong, Lu, Mei-Hong
Format: Article
Language:English
Subjects:
Alzheimer Disease - metabolism
Alzheimer's disease
Amyotrophic lateral sclerosis
Animal models
Animals
Biomedical and Life Sciences
Biomedicine
Cell culture
Drug delivery
Drug development
Drugs
Humans
Huntingtons disease
Mitochondria
Mitochondria - metabolism
Mitophagy
Mitophagy - physiology
Movement disorders
Nervous system
Neurodegenerative diseases
Neurological diseases
Neurological disorders
Neurosciences
Neurotoxicity
Parkinson Disease - metabolism
Parkinson's disease
Pharmacology/Toxicology
Quality control
Review
Traumatic brain injury
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Summary:Mitochondria serve as a vital energy source for nerve cells. The mitochondrial network also acts as a defense mechanism against external stressors that can threaten the stability of the nervous system. However, excessive accumulation of damaged mitochondria can lead to neuronal death. Mitophagy is an essential pathway in the mitochondrial quality control system and can protect neurons by selectively removing damaged mitochondria. In most neurological disorders, dysfunctional mitochondria are a common feature, and drugs that target mitophagy can improve symptoms. Here, we reviewed the role of mitophagy in Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, stroke, and traumatic brain injuries. We also summarized drug and non-drug approaches to promote mitophagy and described their therapeutic role in neurological disorders in order to provide valuable insight into the potential therapeutic agents available for neurological disease treatment. However, most studies on mitophagy regulation are based on preclinical research using cell and animal models, which may not accurately reflect the effects in humans. This poses a challenge to the clinical application of drugs targeting mitophagy. Additionally, these drugs may carry the risk of intolerable side effects and toxicity. Future research should focus on the development of safer and more targeted drugs for mitophagy. Graphical abstract
ISSN:0028-1298
1432-1912
DOI:10.1007/s00210-023-02636-w