Abstract Title:

Pivotal role of carnosine in the modulation of brain cells activity: Multimodal mechanism of action and therapeutic potential in neurodegenerative disorders.

Abstract Source:

Prog Neurobiol. 2018 Dec 26. Epub 2018 Dec 26. PMID: 30593839

Abstract Author(s):

Giuseppe Caruso, Filippo Caraci, Renaud B Jolivet

Article Affiliation:

Giuseppe Caruso


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 anddistribution 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 asAlzheimer's disease. We discuss the potential of carnosine in this context and speculate on new preclinical research directions.

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