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REVIEW

The role of amino acid metabolism in neurodegenerative diseases

Christina Bitsina1 ,  Paschalis Theotokis1 ,  Evangelia Kesidou1 ,  Iliana Michailidou1 ,  Ofira Einstein2 ,  Marina Boziki1 ,  Christos Bakirtzis1* ,  Nikolaos Grigoriadis1*
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1 2nd Department of Neurology, AHEPA General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
2 Department of Physical Therapy, Faculty of Health Sciences, Ariel University, West Bank, Israel
GPD 2024, 3(3), 3294 https://doi.org/10.36922/gpd.3294
Submitted: 27 March 2024 | Accepted: 19 June 2024 | Published: 13 September 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

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.

Keywords
Neurodegenerative disorders
Amino acid metabolism
Mechanistic target of rapamycin signaling pathway
General control non-derepressible protein signaling pathway
Metabolomics studies
Amino acid biomarkers
Funding
None.
Conflict of interest
The authors declare that they have no competing interests.
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