Antioxidant and Neuroprotective Effects of Carnosine: Therapeutic Implications in Neurodegenerative Diseases

Solana-Manrique, Cristina; Sanz, Francisco; Martínez-Carrión, Guillermo; Paricio, Nuria

doi:10.3390/antiox11050848

Cited by 42 publications

(21 citation statements)

References 113 publications

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“…These decreased metabolites are mainly amino acids (histamine, taurine, carnosine, creatinine and beta-alanine) and mitochondrial intermediates (acetyl-CoA, succinate). Taurine, carnosine and its precursor beta-alanine have beneficial anti-oxidant properties 61, 62 . The decrease of these amino acids may predispose the female RPE to oxidative damage.…”

Section: Discussionmentioning

confidence: 99%

Tissue-specific sex difference in mouse eye and brain metabolome under fed and fasted states

Saravanan

Roby

et al. 2023

Preprint

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Purpose: Visual physiology and various ocular diseases demonstrate sexual dimorphisms; however, how sex influences metabolism in different eye tissues remains undetermined. This study aims to address common and tissue-specific sex differences in metabolism in the retina, retinal pigment epithelium (RPE), lens and brain under fed and fasted conditions. Methods: After ad libitum fed or deprived of food for 18 hours, mouse eye tissues (retina, RPE/choroid, and lens), brain, and plasma were harvested for targeted metabolomics. The data were analyzed with both Partial least squares-discriminant analysis (PLS-DA) and Volcano Plot analysis. Results: Among 133 metabolites that cover major metabolic pathways, we found 9-45 metabolites that are sex-different in different tissues under the fed state and 6-18 metabolites under the fasted state. Among these sex-different metabolites, 33 were changed in two or more tissues, and 64 were tissue-specific. Pantothenic acid, hypotaurine and 4-hydroxyproline were the top commonly changed metabolites. Lens and retina had the most tissue-specific sex-different metabolites enriched in the metabolism of amino acid, nucleotide, lipids and TCA cycle. Lens and brain had more similar sex-different metabolites than other occular tissues. Female RPE and female brain were more sensitive to fasting with more reduced metabolites in amino acid metabolism, TCA cycle and glycolysis. The plasma had the least sex-different metabolites with very few overlapping changes with tissues. Conclusion: Sex has a strong influence on eye and brain metabolism in tissue-specific and metabolic state-specific manners. Our findings may implicate the sexual dimorphisms in eye physiology and susceptibility to ocular diseases.

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Section: Discussionmentioning

confidence: 99%

Tissue-specific sex difference in mouse eye and brain metabolome under fed and fasted states

Saravanan

Roby

et al. 2023

Preprint

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“…Glutamate dysfunction and dysregulation of the N-methyl-d-aspartate (NMDA) receptor (glutamatergic receptor) are thought to be linked to the pathogenesis of cognitive deficits of schizophrenia [35,36]. L-carnosine is a known antioxidant that is co-localized at glutamatergic synapses, and it helps people with schizophrenia with their deficient cellular antioxidant defences [37][38][39]. Furthermore, L-carnosine has been shown to modulate NMDA receptor activity, lower glutamate levels, and limit glutamate release [40,41].…”

Section: Role Of L-carnosine In Neurodegenerative Disordersmentioning

confidence: 99%

Effect of L-Carnosine in Patients with Age-Related Diseases: A Systematic Review and Meta-Analysis

Sureshkumar¹,

Durairaj²,

Srinivasan³

et al. 2023

Front. Biosci. (Landmark Ed)

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Introduction: L-carnosine has been found to have multimodal activity. Aim: The aim of this review was to find out the efficacy of Lcarnosine in patients with age-related diseases. Methods: Clinical studies evaluated the effect of L-carnosine on cancer, cardiovascular disease, diabetes, and neurodegenerative disorders were searched in electronic bibliographic databases. The protocol has been registered with PROSPERO (CRD42022314033). The revised Cochrane risk of bias tool for randomized trials was used to assess all of the reports for risk of bias. RevMan 5.4 was used to conduct the meta-analysis. Results: Following the screening process, 14 papers were selected for systematic review, with 9 of them being qualified for meta-analysis. Many of the included studies showed that L-carnosine has potential therapeutic activity in age related diseases. Results from the meta-analysis showed that in diabetes mellitus, HbA1c [mean difference (MD) 95% CI = -1.25 (-2.49, -0.022); p = 0.05; p = 0.001; I 2 = 85%] and fasting blood sugar (FBS) [MD 95% CI = -12.44 (-22.44, -2.44); p = 0.01; p = 0.40; I 2 = 0%] and in neurodegenerative disorder, Wechsler Memory Scale Logical Memory 2 (WMS-LM2) [MD 95% CI = 1.34 (0.83, 1.85); p < 0.00001; p = 0.43; I 2 = 0%], showed statistically significant difference, favoring the L-carnosine group over the control group. While in neurodegenerative disorder, Alzheimer 's Disease Assessment Scale (ADAS) [MD 95% CI = 0.98 (-1.55, -0.42); p = 0.0007; p = 0.86; I 2 = 0%] and Back Depression Inventory (BDI) [MD 95% CI = -1.12 (-1.87, -0.37); p = 0.003; p = 0.73; I 2 = 0%] showed statistically significant difference, favoring the control group over L-carnosine group. Conclusions: Clinical studies were conducted to manage chemotherapy induced toxicities and there are no clinical studies available for its anti-cancer use, and the current evidence does not support its use in the treatment of cardiovascular disease.

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“…When considering the anti-inflammatory and antioxidant activity of carnosine in the CNS [ 260 , 261 ], it becomes particularly interesting to examine if its multimodal pharmacodynamic profile also includes the regulation of Cxs and Panxs. This hypothesis starts from the evidence that carnosine has demonstrated a relevant preclinical efficacy in experimental models of neurodegenerative diseases such as AD and PD, characterized by elevated oxidative stress and inflammation [ 244 , 262 , 263 , 264 , 265 , 266 ] and strongly linked to channel protein complexes dysregulation.…”

Section: Protein Channel Modulation In the Treatment Of Neurodegenera...mentioning

confidence: 99%

Gap Junctions and Connexins in Microglia-Related Oxidative Stress and Neuroinflammation: Perspectives for Drug Discovery

2023

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Microglia represent the immune system of the brain. Their role is central in two phenomena, neuroinflammation and oxidative stress, which are at the roots of different pathologies related to the central nervous system (CNS). In order to maintain the homeostasis of the brain and re-establish the equilibrium after a threatening imbalance, microglia communicate with each other and other cells within the CNS by receiving specific signals through membrane-bound receptors and then releasing neurotrophic factors into either the extracellular milieu or directly into the cytoplasm of nearby cells, such as astrocytes and neurons. These last two mechanisms rely on the activity of protein structures that enable the formation of channels in the membrane, namely, connexins and pannexins, that group and form gap junctions, hemichannels, and pannexons. These channels allow the release of gliotransmitters, such as adenosine triphosphate (ATP) and glutamate, together with calcium ion (Ca2+), that seem to play a pivotal role in inter-cellular communication. The aim of the present review is focused on the physiology of channel protein complexes and their contribution to neuroinflammatory and oxidative stress-related phenomena, which play a central role in neurodegenerative disorders. We will then discuss how pharmacological modulation of these channels can impact neuroinflammatory phenomena and hypothesize that currently available nutraceuticals, such as carnosine and N-acetylcysteine, can modulate the activity of connexins and pannexins in microglial cells and reduce oxidative stress in neurodegenerative disorders.

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Antioxidant and Neuroprotective Effects of Carnosine: Therapeutic Implications in Neurodegenerative Diseases

Cited by 42 publications

References 113 publications

Tissue-specific sex difference in mouse eye and brain metabolome under fed and fasted states

Tissue-specific sex difference in mouse eye and brain metabolome under fed and fasted states

Effect of L-Carnosine in Patients with Age-Related Diseases: A Systematic Review and Meta-Analysis

Gap Junctions and Connexins in Microglia-Related Oxidative Stress and Neuroinflammation: Perspectives for Drug Discovery

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