Could metformin be therapeutically useful in Huntington's disease?

Emerging evidence suggest that dimethylbiguanide (metformin), a first-line drug for type 2 diabetes mellitus, could be neuroprotective in a range of brain pathologies, which include neurodegenerative diseases and brain injury. However, there are also contraindications that associate metformin treatment with cognitive impairment as well as adverse outcomes in Alzheimer's disease and Parkinson's disease animal models. Recently, a beneficial effect of metformin in animal models of Huntington's disease (HD) has been strengthened by multiple reports. In this brief review, the findings associated with the effects of metformin in attenuating neurodegenerative diseases are discussed, focusing on HD-associated pathology and the potential underlying mechanisms highlighted by these studies. The mechanism of action of metformin is complex, and its therapeutic efficacy is therefore expected to be dependent on the disease context. The key metabolic pathways that are effectively affected by metformin, such as AMP-activated protein kinase activation, may be altered in the later decades of the human lifespan. In this regard, metformin may nonetheless be therapeutically useful for neurological diseases with early pathological onsets, such as HD.