中国神经再生研究(英文版) ›› 2024, Vol. 19 ›› Issue (5): 1045-1055.doi: 10.4103/1673-5374.385286

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

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  • 出版日期:2024-05-15 发布日期:2023-10-31

Promising use of metformin in treating neurological disorders: biomarker-guided therapies

Allison Loan1, 2, #, Charvi Syal1, #, Margarita Lui1, Ling He3, *, Jing Wang1, 4, 5, *   

  1. 1Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada; 2Department of Biology, Faculty of Science, University of Ottawa, Ottawa, ON, Canada; 3Department of Pediatrics and Medicine, Johns Hopkins Medical School, Baltimore, MD, USA; 4Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada; 5University of Ottawa Brain and Mind Research Institute, Ottawa, ON, Canada
  • Online:2024-05-15 Published:2023-10-31
  • Contact: Jing Wang, PhD, jiwang@ohri.ca; Ling He, PhD, heling@jhmi.edu.

摘要: https://orcid.org/0000-0003-2410-4771 (Jing Wang); https://orcid.org/0000-0001-7038-5848 (Ling He)

Abstract: Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases (Alzheimer’s disease, multiple sclerosis, Parkinson’s disease, Huntington’s disease), cerebrovascular conditions (stroke), and neurodevelopmental disorders (autism spectrum disorder). Although they affect millions of individuals around the world, only a limited number of effective treatment options are available today. Since most neurological disorders express mitochondria-related metabolic perturbations, metformin, a biguanide type II antidiabetic drug, has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy metabolism. However, controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological disorders. Given that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging, lifestyle, genetics, and environment, it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological disorders. These molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment, ultimately developing targeted therapy. In this review, we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.

Key words: Alzheimer’s disease, Huntington’s disease, metformin, mitochondrial perturbation, multiple sclerosis, neural degenerative diseases, Parkinson’s disease, stroke, targeted therapy