Synergistic association of resveratrol and histone deacetylase inhibitors as treatment in amyotrophic lateral sclerosis.

Autor:	Parrella E; Division of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy., Porrini V; Division of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy., Scambi I; Section of Anatomy and Histology, Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy., Gennari MM; Division of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy., Gussago C; Division of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy., Bankole O; Section of Anatomy and Histology, Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy., Benarese M; Division of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy., Mariotti R; Section of Anatomy and Histology, Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy., Pizzi M; Division of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2022 Oct 21; Vol. 13, pp. 1017364. Date of Electronic Publication: 2022 Oct 21 (Print Publication: 2022).
DOI:	10.3389/fphar.2022.1017364
Abstrakt:	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. Competing Interests: 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. (Copyright © 2022 Parrella, Porrini, Scambi, Gennari, Gussago, Bankole, Benarese, Mariotti and Pizzi.)
Databáze:	MEDLINE
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