Neuroprotective features of carnosine in oxidative driven diseases

Carnosine analogues containing NO-donor substructures: Synthesis, physico-chemical characterization and preliminary pharmacological profile

“…In our acute experimental model, the potential further beneficial effect of NO release by compound 7e was blunted by the predominant role of antioxidant activity due to the carnosine amide substructure. This observation is in keeping with previous in vivo and in vitro studies reporting that carnosine neuroprotective effects were almost entirely attributable to its ability to inhibit and/or prevent oxidative and nitrosative stress [13]. However, recently, carnosine has also been demonstrated to reduce glutamate excitotoxicity through the regulation of the glutamate transporter-1 [50], to protect the bioelectric activity of nervous cells by restoring the activity of the glutamatergic and GABAergic receptors [53] and to affect the apoptotic cascade in the ischemic brain by inhibiting mRNA expression of apoptosis-inducing factor and caspase-3 [51].…”

“…Since oxidative stress and AGEs are involved in the development and progression of some cardiovascular and neurodegenerative diseases [11,12], as well as in ageing, there is currently great interest in carnosine and its derivatives. Recently the effects of carnosine have been extensively studied both in vivo and in vitro in different models of oxidative driven damages, such as neurodegenerative disorders and hypoxia-ischemic injuries [13]. L-carnosine dietary supplementation proved able to promote a strong reduction in the hippocampal intraneuronal Aaccumulation, and to rescue AD and ageing-related mithocondrial disfunction in 3xTG-AD mice [14].…”

Oxaliplatin complexes with carnosine and its derivatives: in vitro cytotoxicity, mass spectrometric and computational studies with a focus on complex fragmentation

“…[29,30] In the skeletal muscle and nerve cells it is found at concentrations of up to 20 mM. [31,32] Since its discovery there have been many investigations into its biological function and it is now known that carnosine acts as an anti-oxidant, scavenger of free radicals and active oxygen species [30], as a biological buffer, a source for histidine, an immunostimulant and transition metal ion chelator, especially for Zn 2+ and Cu 2+ [33] and heavy metals. [34] The ability of carnosine to bind Zn 2+ helps modulate neuronal excitability by preventing the Zn 2+ inhibition of neurotransmitter receptors.…”

Carnosine and Related Peptides: Therapeutic Potential in Age-Related Disorders

“…Pretreatment of rat brain endothelial cells with carnosine (20 mM) also protected them against the toxicity mediated by an Aβ peptide fragment (residues [25][26][27][28][29][30][31][32][33][34][35] [49,82]. Similarly, a set of in vivo experiments showed that 3xTg-AD mice receiving carnosine orally exhibited strong reduction of the hippocampal intraneuronal accumulation of Aβ and improvement of mitochondrial dysfunction related to aging and AD: recovery of the complexes II and IV activities in hippocampus and recovery of the complexes I and IV activities in cerebral cortex [84].…”

“…It has been suggested that carnosine may be involved in the prevention and therapy of oxidative driven disorders, including neurodegenerative diseases and hypoxicischemic damage of CNS [29]. The major risk factor to neurodegenerative disorders is aging, and mitochondria were implicated in such phenomenon through mechanisms that include accumulation of mutations in mitochondrial DNA (mtDNA) and reactive oxygen species (ROS) generation [30].…”