Restoring the epigenome in Alzheimer's disease: advancing HDAC inhibitors as therapeutic agents.

Drug Discov Today 2024

Pereira M, Cruz MT, Fortuna A

Abstract

  1. Drug Discov Today. 2024 Jul;29(7):104052. doi: 10.1016/j.drudis.2024.104052. Epub 2024 Jun 1.

Restoring the epigenome in Alzheimer’s disease: advancing HDAC inhibitors as therapeutic agents.

Pereira M(1), Cruz MT(2), Fortuna A(3), Bicker J(4).

Author information: (1)University of Coimbra, Faculty of Pharmacy, Coimbra, Portugal. (2)University of Coimbra, Faculty of Pharmacy, Coimbra, Portugal; University of Coimbra, Center for Neuroscience and Cell Biology, Coimbra, Portugal. (3)University of Coimbra, Faculty of Pharmacy, Coimbra, Portugal; University of Coimbra, Coimbra Institute for Biomedical Imaging and Translational Research, Coimbra, Portugal. (4)University of Coimbra, Faculty of Pharmacy, Coimbra, Portugal; University of Coimbra, Coimbra Institute for Biomedical Imaging and Translational Research, Coimbra, Portugal. Electronic address: joana.bicker@gmail.com.

Current treatment options for Alzheimer’s disease (AD) focus on symptom relief rather than halting disease progression. In this context, targeting histone deacetylation emerges as a promising therapeutic alternative. Dysregulation of histone deacetylase (HDAC) activity is present in AD, contributing to cognitive decline. Pharmacological HDAC inhibition has shown benefits in preclinical models, namely reduced amyloid beta plaque formation, lower phosphorylation and aggregation of tau protein, greater microtubule stability, less neuroinflammation, and improved metabolic homeostasis and cell survival. Nonetheless, clinical trials evidenced limitations such as insufficient selectivity or blood-brain barrier penetration. Hence, future innovative strategies are required to enhance their efficacy/safety.

Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.

DOI: 10.1016/j.drudis.2024.104052 PMID: 38830501 [Indexed for MEDLINE]

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