Effects of dietary supplementation of carnosine on mitochondrial dysfunction, amyloid pathology, and cognitive deficits in 3xTg-AD mice.

<h4>Background</h4>The pathogenic road map leading to Alzheimer's disease (AD) is still not completely understood; however, a large body of studies in the last few years supports the idea that beside the classic hallmarks of the disease, namely the accumulation of amyloid-β (Aβ) and...

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Autores principales: Carlo Corona, Valerio Frazzini, Elena Silvestri, Rossano Lattanzio, Rossana La Sorda, Mauro Piantelli, Lorella M T Canzoniero, Domenico Ciavardelli, Enrico Rizzarelli, Stefano L Sensi
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2011
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Acceso en línea:https://doaj.org/article/6876e911f0ea48ffb015201abbaffa04
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Sumario:<h4>Background</h4>The pathogenic road map leading to Alzheimer's disease (AD) is still not completely understood; however, a large body of studies in the last few years supports the idea that beside the classic hallmarks of the disease, namely the accumulation of amyloid-β (Aβ) and neurofibrillary tangles, other factors significantly contribute to the initiation and the progression of the disease. Among them, mitochondria failure, an unbalanced neuronal redox state, and the dyshomeostasis of endogenous metals like copper, iron, and zinc have all been reported to play an important role in exacerbating AD pathology. Given these factors, the endogenous peptide carnosine may be potentially beneficial in the treatment of AD because of its free-radical scavenger and metal chelating properties.<h4>Methodology</h4>In this study, we explored the effect of L-carnosine supplementation in the 3xTg-AD mouse, an animal model of AD that shows both Aβ- and tau-dependent pathology.<h4>Principal findings</h4>We found that carnosine supplementation in 3xTg-AD mice promotes a strong reduction in the hippocampal intraneuronal accumulation of Aβ and completely rescues AD and aging-related mitochondrial dysfunctions. No effects were found on tau pathology and we only observed a trend toward the amelioration of cognitive deficits.<h4>Conclusions and significance</h4>Our data indicate that carnosine can be part of a combined therapeutic approach for the treatment of AD.