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.

Important roles of dietary taurine, creatine, carnosine, anserine and 4-hydroxyproline in human nutrition and health

“…In addition, being a positively charged dipeptide that is resistant to peptidases, carnosine does not readily exit cells and can be accumulated inside the cells at high concentrations within physiological ranges. Through its intracellular actions, carnosine confers a vasorelaxing effect to reduce blood pressure (Ririe et al 2000), stroke, and seizures (Horning et al 2000), and carnosine is particularly beneficial for ameliorating ageing-related disorders such as cataract and neurological diseases (Cararo et al 2015;Schön et al 2019). Thus, carnosine plays an important role in maintaining cell structure and function, as well as whole-body homeostasis and healthy aging, while reducing the risk of oxidative stress-related diseases, such as obesity, diabetes, hypertension, atherosclerosis, Alzheimer's disease, stroke and seizures.…”

Modulation of Pro-Oxidant and Pro-Inflammatory Activities of M1 Macrophages by the Natural Dipeptide Carnosine

“…brain (micromolar to millimolar range) [26,27], but it reaches its maximal concentrations in cardiac and skeletal muscles (up to 20 mM) [28]. Furthermore, strong evidence that carnosine protects against pathologies characterized by oxidative stress and/or inflammation such as diabetes [29], depression [30], cerebral ischemia [31] and Alzheimer's disease (AD) [32] has been proved.…”

GADL1 is a multifunctional decarboxylase with tissue-specific roles in β-alanine and carnosine production

“…Since Gadl1 -/mice displayed behavioral changes and β-alanine and carnosine peptides have been implicated in many different physiological functions and disease states, we performed a gene-based analysis of GADL1 and enzymes and transporters directly involved in carnosine metabolism. We selected 19 human diseases and traits related to oxidative stress and where treatment with carnosine peptides have shown some promising effects (13) (Fig. 8).…”

“…cDNA was synthesized in triplicates from this RNA using a High-Capacity RNA-to-cDNA™ Kit (#4387406, Applied Biosystems™). qRT-PCR was performed using the TaqMan gene expression assay (TaqMan Gene Expression Master Mix #4369016, Applied Biosystems™) The TaqMan probes were: Mm00520087_m1 (CSAD), Mm01348767_m1 (GADL1, exon [13][14], Mm01341531_m1 (GADL1, exon 3-4), Mm01341534_m1 (GADL1, exon 6-7), Mm99999915_g1 (GAPDH) and Mm00607939_s1 (β-actin). mRNA expression for all genotypes was normalized against the housekeeping genes GAPDH and β-actin using a variant (2 ΔCt ) of the Livak Method (2 -ΔΔCt ) as described in the Real-Time PCR applications guide from Bio-Rad (56).…”

“…Such findings have led to the widespread use of dietary β-alanine supplements, particularly among athletes and soldiers (10). β-alanine and carnosine dietary supplementation have also shown some promising effects in the treatment of depression, anxiety and autism symptoms in humans (11) and animal models (12,13).…”