Synergistic association of resveratrol and histone deacetylase inhibitors as treatment in amyotrophic lateral sclerosis.
NF-κB/RelA
amyotrophic lateral sclerosis (ALS)
epigenetic drugs
histone acetylation
histone deacetylase (HDAC) inhibitors
resveratrol
sexual dimorphism
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2022
2022
Historique:
received:
11
08
2022
accepted:
06
10
2022
entrez:
7
11
2022
pubmed:
8
11
2022
medline:
8
11
2022
Statut:
epublish
Résumé
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with motor neuron degeneration, progressive paralysis and finally death. Despite the research efforts, currently there is no cure for ALS. In recent years, multiple epigenetic mechanisms have been associated with neurodegenerative diseases. A pathological role for histone hypoacetylation and the abnormal NF-κB/RelA activation involving deacetylation of lysines, with the exclusion of lysine 310, has been established in ALS. Recent findings indicate that the pathological acetylation state of NF-κB/RelA and histone 3 (H3) occurring in the SOD1(G93A) murine model of ALS can be corrected by the synergistic combination of low doses of the AMP-activated kinase (AMPK)-sirtuin 1 pathway activator resveratrol and the histone deacetylase (HDAC) inhibitors MS-275 (entinostat) or valproate. The combination of the epigenetic drugs, by rescuing RelA and the H3 acetylation state, promotes a beneficial and sexually dimorphic effect on disease onset, survival and motor neurons degeneration. In this mini review, we discuss the potential of the epigenetic combination of resveratrol with HDAC inhibitors in the ALS treatment.
Identifiants
pubmed: 36339574
doi: 10.3389/fphar.2022.1017364
pii: 1017364
pmc: PMC9633661
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
1017364Informations de copyright
Copyright © 2022 Parrella, Porrini, Scambi, Gennari, Gussago, Bankole, Benarese, Mariotti and Pizzi.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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