Potential roles of branched-chain amino acids in neurodegeneration

•Branched-chain amino acids (BCAAs) can induce excitotoxicity, hyperexcitability, inflammation, and oxidative stress and may contribute to the development of neurodegenerative diseases.•BCAA consumption can influence neurotransmitter levels in the central nervous system and may result in dysregulation of neurotrophic factors.•BCAAs and BCAA metabolism may be involved in the pathogenesis of major neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases and amyotrophic lateral sclerosis.•Deciphering the potential roles of BCAAs in neurodegeneration may allow for identifying new therapeutic targets for neurodegenerative diseases. 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.