The role of amino acid metabolism in neurodegenerative diseases

The exact etiologies of most neurodegenerative disorders remain poorly understood, therefore hampering the identification of molecular targets with clinical therapeutic potential. Recent clinical and experimental evidence supports the notion that amino acid metabolism could be implicated in the pathophysiology and disease progression of neurodegenerative diseases. This review aims to present the most common neurological diseases that lead to axonal degeneration and to examine the potential role of amino acid metabolism, with a particular focus on multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. The primary objective of this study is to identify potential amino acid biomarkers through metabolomics research and to propose therapeutic approaches by modulating amino acid-sensing signaling pathways to effectively monitor disease progression in neurodegenerative disorders. In this context, two distinct cellular signaling pathways are examined: the mechanistic target of rapamycin signaling pathway and the general control non-derepressible protein-integrated stress response pathway. These signaling cascades are analyzed in relation to each of the aforementioned neurological disorders to identify their potential regulatory roles in disease progression and pathophysiology. The review concludes by considering emerging amino acid biomarkers with potential clinical and diagnostic value, exploring signaling cascades for therapeutic manipulation to improve clinical outcomes in neurodegeneration, and providing insights for future research in the biomedical field.