Cargando…

Histone Deacetylase Inhibitors and Diabetic Kidney Disease

Despite recent clinical trial advances and improvements in clinical care, kidney disease due to diabetes remains the most common cause of chronic kidney failure worldwide. In the search for new treatments, recent attentions have turned to drug repurposing opportunities, including study of the histon...

Descripción completa

Detalles Bibliográficos
Autores principales: Hadden, Mitchell J., Advani, Andrew
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165182/
https://www.ncbi.nlm.nih.gov/pubmed/30189630
http://dx.doi.org/10.3390/ijms19092630
_version_ 1783359776524075008
author Hadden, Mitchell J.
Advani, Andrew
author_facet Hadden, Mitchell J.
Advani, Andrew
author_sort Hadden, Mitchell J.
collection PubMed
description Despite recent clinical trial advances and improvements in clinical care, kidney disease due to diabetes remains the most common cause of chronic kidney failure worldwide. In the search for new treatments, recent attentions have turned to drug repurposing opportunities, including study of the histone deacetylase (HDAC) inhibitor class of agents. HDACs are a group of enzymes that remove functional acetyl groups from histone and non-histone proteins and they can affect cellular function through both epigenetic and non-epigenetic means. Over the past decade, several HDAC inhibitors have been adopted into clinical practice, primarily for the treatment of hematological malignancy, whereas other existing therapies (for instance valproate) have been found to have HDAC inhibitory effects. Here we review the current HDAC inhibitors in the clinic and under development; the literature evidence supporting the renoprotective effects of HDAC inhibitors in experimental diabetic kidney disease; and the adverse effect profiles that may prevent existing therapies from entering the clinic for this indication. Whereas recent research efforts have shed light on the fundamental actions of HDACs in the diabetic kidney, whether these efforts will translate into novel therapies for patients will require more specific and better-tolerated therapies.
format Online
Article
Text
id pubmed-6165182
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-61651822018-10-10 Histone Deacetylase Inhibitors and Diabetic Kidney Disease Hadden, Mitchell J. Advani, Andrew Int J Mol Sci Review Despite recent clinical trial advances and improvements in clinical care, kidney disease due to diabetes remains the most common cause of chronic kidney failure worldwide. In the search for new treatments, recent attentions have turned to drug repurposing opportunities, including study of the histone deacetylase (HDAC) inhibitor class of agents. HDACs are a group of enzymes that remove functional acetyl groups from histone and non-histone proteins and they can affect cellular function through both epigenetic and non-epigenetic means. Over the past decade, several HDAC inhibitors have been adopted into clinical practice, primarily for the treatment of hematological malignancy, whereas other existing therapies (for instance valproate) have been found to have HDAC inhibitory effects. Here we review the current HDAC inhibitors in the clinic and under development; the literature evidence supporting the renoprotective effects of HDAC inhibitors in experimental diabetic kidney disease; and the adverse effect profiles that may prevent existing therapies from entering the clinic for this indication. Whereas recent research efforts have shed light on the fundamental actions of HDACs in the diabetic kidney, whether these efforts will translate into novel therapies for patients will require more specific and better-tolerated therapies. MDPI 2018-09-05 /pmc/articles/PMC6165182/ /pubmed/30189630 http://dx.doi.org/10.3390/ijms19092630 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Hadden, Mitchell J.
Advani, Andrew
Histone Deacetylase Inhibitors and Diabetic Kidney Disease
title Histone Deacetylase Inhibitors and Diabetic Kidney Disease
title_full Histone Deacetylase Inhibitors and Diabetic Kidney Disease
title_fullStr Histone Deacetylase Inhibitors and Diabetic Kidney Disease
title_full_unstemmed Histone Deacetylase Inhibitors and Diabetic Kidney Disease
title_short Histone Deacetylase Inhibitors and Diabetic Kidney Disease
title_sort histone deacetylase inhibitors and diabetic kidney disease
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165182/
https://www.ncbi.nlm.nih.gov/pubmed/30189630
http://dx.doi.org/10.3390/ijms19092630
work_keys_str_mv AT haddenmitchellj histonedeacetylaseinhibitorsanddiabetickidneydisease
AT advaniandrew histonedeacetylaseinhibitorsanddiabetickidneydisease