Neuroprotective Effect of Carnosine Is Mediated by Insulin-Degrading Enzyme

Distefano, Alessia; Caruso, Giuseppe; Oliveri, Valentina; Bellia, Francesco; Sbardella, Diego; Zingale, Gabriele Antonio; Caraci, Filippo; Grasso, Giuseppe

doi:10.1021/acschemneuro.2c00201

Cited by 13 publications

(12 citation statements)

References 62 publications

(98 reference statements)

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“…Carnosine has been shown to stimulate its activity towards not only Aβ but also insulin, both of which are the so called long-substrates of the enzyme. One of the mechanisms proposed is the modulation that carnosine may have in favoring the oligomerization and therefore the activation of the IDE, finally preventing Aβ-induced toxicity in neuronal cultures ( Distefano et al., 2022 ).…”

Section: Cellular and Molecular Mechanisms Modulated By Carnosinementioning

confidence: 99%

The therapeutic potential of carnosine: Focus on cellular and molecular mechanisms

Caruso

Pietro

Cardaci

et al. 2023

Current Research in Pharmacology and Drug Discovery

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Section: Cellular and Molecular Mechanisms Modulated By Carnosinementioning

confidence: 99%

The therapeutic potential of carnosine: Focus on cellular and molecular mechanisms

Caruso

Pietro

Cardaci

et al. 2023

Current Research in Pharmacology and Drug Discovery

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“…In fact, the accumulation of Aβ plaques and α-synuclein, the clinical hallmarks of AD and PD, respectively, are associated with increased levels of Cx43 and chronic activation of the HCs they form. In particular, concerning AD, increased Cx43 HC activity has been shown to occur in microglia, neurons, and astrocytes after stimulation with Aβ oligomers, known to be the most toxic species of Aβ aggregates [ 162 , 224 ]. Moreover, in Huntington’s disease, increased Cx43 GJs have been related to the mitochondrial fragmentation deriving from the abnormally long polyglutamine found in the HTT protein [ 223 ].…”

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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“…Carnosine (β-alanyl- l -histidine) is an endogenous dipeptide that is characterized by a high therapeutic potential, being a well-known antioxidant and also having metal chelating, anti-aggregating, anti-inflammatory, and neuroprotective properties [ 8 , 9 ]. Due to its multimodal mechanism of action, including its ability to improve intramuscular buffering capacity (suppressing acidosis), carnosine has already been considered as a “natural endogenous antidote”.…”

Section: Introductionmentioning

confidence: 99%

The Therapeutic Potential of Carnosine as an Antidote against Drug-Induced Cardiotoxicity and Neurotoxicity: Focus on Nrf2 Pathway

et al. 2022

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Different drug classes such as antineoplastic drugs (anthracyclines, cyclophosphamide, 5-fluorouracil, taxanes, tyrosine kinase inhibitors), antiretroviral drugs, antipsychotic, and immunosuppressant drugs are known to induce cardiotoxic and neurotoxic effects. Recent studies have demonstrated that the impairment of the nuclear factor erythroid 2–related factor 2 (Nrf2) pathway is a primary event in the pathophysiology of drug-induced cardiotoxicity and neurotoxicity. The Nrf2 pathway regulates the expression of different genes whose products are involved in antioxidant and inflammatory responses and the detoxification of toxic species. Cardiotoxic drugs, such as the anthracycline doxorubicin, or neurotoxic drugs, such as paclitaxel, suppress or impair the Nrf2 pathway, whereas the rescue of this pathway counteracts both the oxidative stress and inflammation that are related to drug-induced cardiotoxicity and neurotoxicity. Therefore Nrf2 represents a novel pharmacological target to develop new antidotes in the field of clinical toxicology. Interestingly, carnosine (β-alanyl-l-histidine), an endogenous dipeptide that is characterized by strong antioxidant, anti-inflammatory, and neuroprotective properties is able to rescue/activate the Nrf2 pathway, as demonstrated by different preclinical studies and preliminary clinical evidence. Starting from these new data, in the present review, we examined the evidence on the therapeutic potential of carnosine as an endogenous antidote that is able to rescue the Nrf2 pathway and then counteract drug-induced cardiotoxicity and neurotoxicity.

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Neuroprotective Effect of Carnosine Is Mediated by Insulin-Degrading Enzyme

Cited by 13 publications

References 62 publications

The therapeutic potential of carnosine: Focus on cellular and molecular mechanisms

The therapeutic potential of carnosine: Focus on cellular and molecular mechanisms

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

The Therapeutic Potential of Carnosine as an Antidote against Drug-Induced Cardiotoxicity and Neurotoxicity: Focus on Nrf2 Pathway

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