Evidence map›Paper›PMID 41594643›Full record

ReviewBiomolecules2026

Epigenetic Dysregulation in Neurodegeneration: The Role of Histone Deacetylases and Emerging Inhibitor Strategies.

Yogesh Pawar, Aleksandra Kopranovic, Ramaa C S, Franz-Josef Meyer-Almes

Abstract readReview
In one paragraph

Review in Biomolecules, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Yogesh PawarDepartment of Pharmaceutical Chemistry, Bharati Vidyapeeth's College of Pharmacy, CBD Belapur, Navi Mumbai 400614, India.ORCID 0009-0005-6564-8603
Aleksandra KopranovicDepartment of Chemical Engineering and Biotechnology, University of Applied Science, 64290 Darmstadt, Germany.
Ramaa C SDepartment of Pharmaceutical Chemistry, Bharati Vidyapeeth's College of Pharmacy, CBD Belapur, Navi Mumbai 400614, India.
Franz-Josef Meyer-AlmesDepartment of Chemical Engineering and Biotechnology, University of Applied Science, 64290 Darmstadt, Germany.ORCID 0000-0002-1001-3249

Funding

Darmstadt University of Applied Sciences none
6 · The paper itself

Abstract

Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) are characterized by complex pathologies with progressive neurodegeneration, protein misfolding, oxidative stress, and persistent inflammation. Recent findings indicate the pivotal involvement of epigenetic disruption, particularly aberrant histone deacetylase (HDAC) activity, in disease initiation and progression. In the current review, we systematically discuss the mechanistic function of HDACs across all classes (I, IIa, IIb, III, and IV) in neurodegenerative disease mechanisms, such as their involvement in the modulation of gene expression, mitochondrial function, proteostasis, and neuronal survival. We discuss the therapeutic potential, as well as limitations, of HDAC inhibitors (HDACis), such as pan-inhibitors and isoenzyme-selective inhibitors, and new multi-target-directed ligands with HDAC inhibition combined with acetylcholinesterase modulation, PDE modulation, MAO-B inhibition, or NMDAR modulation. Particular emphasis is placed on the development of HDAC6-selective inhibitors with enhanced brain permeability and reduced toxicity, which have shown promising preclinical efficacy in ameliorating hallmark pathologies of AD, PD, and HD. In addition, s-triazine-based scaffolds have recently emerged as promising chemotypes in HDAC inhibitor design, offering favorable pharmacokinetic profiles, metabolic stability, and the potential for dual-target modulation relevant to neurodegeneration. The review also explores the future of HDAC-targeted therapies, including PROTAC degraders, dual-inhibitor scaffolds, and sustainable, BBB-penetrant molecules. Collectively, this review underscores the importance of HDAC modulation as a multifaceted strategy in the treatment of neurodegenerative diseases and highlights the need for continued innovation in epigenetic drug design.

Indexed as

Epigenesis, GeneticHistone Deacetylase InhibitorsHistone DeacetylasesNeurodegenerative DiseasesAnimalsHumansHistone Deacetylase InhibitorsHistone DeacetylasesAlzheimer’s disease (AD)blood–brain barrier permeabilityglioblastomahistone deacetylase inhibitors (HDACis)Huntington’s disease (HD)multi-target-directed ligands (MTDLs)neurodegenerative diseasesParkinson’s disease (PD)s-traizine

Identifiers

PMID41594643
PMCPMC12839100

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.