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Pivotal role of carnosine in the modulation of brain cells activity: Multimodal mechanism of action and therapeutic potential in neurodegenerative disorders
Abstract
Carnosine (β-alanyl-l-histidine), a dipeptide, is an endogenous antioxidant widely distributed in excitable tissues like muscles and the brain. Although discovered more than a hundred years ago and having been extensively studied in the periphery, the role of carnosine in the brain remains mysterious. Carnosinemia, a rare metabolic disorder with increased levels of carnosine in urine and low levels or absence of carnosinase in the blood, is associated with severe neurological symptoms in humans. This review deals with the role of carnosine in the brain in both physiological and pathological conditions, with a focus on preclinical evidence suggesting a high therapeutic potential of carnosine in neurodegenerative disorders. We review carnosine and carnosinemia's discoveries and the extensive research on the role and benefits of carnosine in the periphery. We then turn to carnosine's biochemistry and distribution in the brain. Using an array of recent observations as a foundation, we draw a parallel with the role of carnosine in muscles and speculate on the role of carnosine in promoting the metabolic support of neurons by glial cells. Finally, carnosine has been shown to exert a multimodal activity including inhibition of protein cross-linking and aggregation of amyloid-β and related proteins, free radical generation, nitric oxide detoxification, and an anti-inflammatory activity. It could thus play an important role in the prevention and treatment of neurodegenerative diseases such as Alzheimer's disease. We discuss the potential of carnosine in this context and speculate on new preclinical research directions.
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“Carnosine-Niosomal Delivery System for Targeted Cancer Therapy”
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Metadata
- Authors
- Caruso, G., Caraci, F., & Jolivet, R. B.
- Affiliations
- I.R.C.C.S. Oasi Maria SS (IT)
- University of Catania (IT)
- University of Geneva (CH)
- Corresponding author
- Caruso, Giuseppe
- Caraci, Filippo
- Jolivet, Renaud B.
- Venue
- Progress in Neurobiology
- Publisher
- Elsevier BV
- Published
- 2019-04
- Volume
- 175
- Pages
- 35-53
- ISSN
- 0301-0082 (ISSN-L)
- OpenAlex
- W2905996342
- Cited by
- 110
- References
- 299
- Citations by year
- 2026: 8 · 2025: 15 · 2024: 17 · 2023: 18 · 2022: 17 · 2021: 11 · 2020: 13 · 2019: 11
- FWCI
- 1.15
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Swiss National Science Foundation (31003A_170079)
- Australian Research Council (DP180101494)
- Italian Ministry of Health Research Program 2018 (2635256)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Biochemical effects in animals
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Polyamine Metabolism and Applications
- Keywords
- carnosine, carnosinase, neurodegenerative diseases, Alzheimer's disease, brain, glial cells, neuroprotection, amyloid-beta aggregation, protein cross-linking, nitric oxide detoxification, free radicals, anti-inflammatory activity, antioxidants
- MeSH terms
- Amino Acid Metabolism, Inborn Errors, Animals, Brain, Carnosine, Dipeptidases, Humans, Neurodegenerative Diseases, Brain Diseases, Metabolic, Inborn
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