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The Potential of Carnosine in Brain-Related Disorders: A Comprehensive Review of Current Evidence.

ABSTRACT: Neurological, neurodegenerative, and psychiatric disorders represent a serious burden because of their increasing prevalence, risk of disability, and the lack of effective causal/disease-modifying treatments. There is a growing body of evidence indicating potentially favourable effects of carnosine, which is an over-the-counter food supplement, in peripheral tissues. Although most studies to date have focused on the role of carnosine in metabolic and cardiovascular disorders, the physiological presence of this di-peptide and its analogues in the brain together with their ability to cross the blood-brain barrier as well as evidence from in vitro, animal, and human studies suggest carnosine as a promising therapeutic target in brain disorders. In this review, we aim to provide a comprehensive overview of the role of carnosine in neurological, neurodevelopmental, neurodegenerative, and psychiatric disorders, summarizing current evidence from cell, animal, and human cross-sectional, longitudinal studies, and randomized controlled trials.

SUBMITTER: Schon M

PROVIDER: S-EPMC6627134 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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The Potential of Carnosine in Brain-Related Disorders: A Comprehensive Review of Current Evidence.

Schön Martin M Mousa Aya A Berk Michael M Chia Wern L WL Ukropec Jozef J Majid Arshad A Ukropcová Barbara B de Courten Barbora B

Nutrients 20190528 6

Neurological, neurodegenerative, and psychiatric disorders represent a serious burden because of their increasing prevalence, risk of disability, and the lack of effective causal/disease-modifying treatments. There is a growing body of evidence indicating potentially favourable effects of carnosine, which is an over-the-counter food supplement, in peripheral tissues. Although most studies to date have focused on the role of carnosine in metabolic and cardiovascular disorders, the physiological p ...[more]

PMID: 31141890

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Project description:Background:The electrophysiological evidence supporting the therapeutic efficacy of multiple transcranial direct current stimulation (tDCS) sessions on consciousness improvement in patients with prolonged disorders of consciousness (DOCs) has not been firmly established. Objectives:To assess the effects of repeated tDCS in patients with prolonged DOCs by Coma Recovery Scale-Revised (CRS-R) score and event-related potential (ERP). Method:Using a sham-controlled randomized double-blind design, 26 patients were randomly assigned to either a real [five vegetative state (VS) and eight minimally conscious state (MCS) patients] or sham (six VS and seven MCS patients) stimulation group. The patients in the real stimulation group underwent 20 anodal tDCS sessions of the left dorsolateral prefrontal cortex (DLPFC) over 10 consecutive working days. The CRS-R score and P300 amplitude and latency in a hierarchical cognitive assessment were recorded to evaluate the consciousness level before tDCS and immediately after the 20 sessions. Results:The intra-group CRS-R analysis revealed a clinically significant improvement in the MCS patients in the real stimulation group. The inter-group CRS-R analysis showed a significant difference in CRS-R between VS and MCS patients at baseline in both the real and sham stimulation groups. The intra-group ERP analysis revealed a significant increase in P300 amplitude after tDCS in the MCS patients in the real stimulation group, but no significant differences in P300 latency. For the inter-group ERP analysis, we observed significant differences regarding the presence of P300 at baseline between the VS and MCS patients in both groups. Conclusion:The repeated anodal tDCS of the left DLPFC could produce clinically significant improvements in MCS patients. The observed tDCS-related consciousness improvements might be related to improvements in attention resource allocation (reflected by the P300 amplitude). The findings support the use of tDCS in clinical practice and ERP might serve as an efficient electrophysiological assessment tool in patients with DOCs.

Project description:Interactive relationships among metabolism, mitochondrial dysfunction and inflammation at skeletal muscle level play a key role in the pathogenesis of disorders related to oxidative stress. Mitochondrial dysfunction and oxidative stress result in cellular energy deficiency, inflammation and cell death inducing a vicious cycle that promotes muscle wasting. The histidine-containing dipeptides, carnosine and anserine, are carbonyl scavengers whose cytoprotective contributions extend beyond the antioxidant defence, but the physiological meaning of these capacities is actually limited. In the present study, we compared and investigated the potential protective effects of three different histidine-containing dipeptides: carnosine, anserine and carnosinol, a carnosine-mimetic new compound, against oxidative stress induction in rat L6 skeletal muscle cells. The hydrogen peroxide induced-oxidative stress significantly altered cell morphology, induced apoptosis, oxidative stress and inflammation, decreased mitochondrial peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α)/sirtuin3 pathway and the antioxidant system. Notably, all three investigated dipeptides in the present study, with a different extent and in a concentration-dependent manner, reduced myotube oxidative stress, apoptosis and inflammation. The present study underlined that carnosinol, maintaining the safety condition of carnosine and anserine, was the more efficient studied dipeptide in the preservation of mitochondrial environment mediated by PGC-1α and sirtuin3 expression and thereby in the reduction of oxidative stress-related alterations in this in vitro skeletal muscle model. Furthermore, we observed that carnosinol's antioxidant effects are not blocked inhibiting sirtuin3, but are maintained with almost the same extend, indicating its multiple capacities of reactive carbonyl species-scavenging and of mitochondrial modulation through PGC-1α. In conclusion, carnosinol retained and surpassed the efficacy of the well-known investigated histidine-containing dipeptides improving oxidative stress, inflammation and also cell metabolism and so becoming a greatly promising therapeutic carnosine derivate.

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The Potential of Carnosine in Brain-Related Disorders: A Comprehensive Review of Current Evidence.

Publications

The Potential of Carnosine in Brain-Related Disorders: A Comprehensive Review of Current Evidence.

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