Potential roles of branched-chain amino acids in neurodegeneration

Despite having disease-specific pathologic features and symptoms, neurodegenerative diseases share common mechanisms, such as excitotoxicity, neuroinflammation, and neurotransmitter dysregulation. Although the common underlying cause of these neurodegenerative processes has yet to be identified, accumulating evidence suggests that branched-chain amino acids (BCAAs) could be involved. BCAAs have been shown to not only influence the central levels of neurotransmitters but also to induce excitotoxicity, hyperexcitability, inflammation, and oxidative stress. Furthermore, emerging evidence indicates that BCAA metabolism may be dysregulated in major neurodegenerative diseases, namely Alzheimer's and Parkinson's diseases and amyotrophic lateral sclerosis. In this review, we identified the neurodegenerative mechanisms of BCAAs and outlined their potential roles in neurodegenerative diseases, suggesting that targeting BCAA metabolism may represent a new approach to identifying new therapeutic targets for multifaceted neurodegenerative diseases.