Therapeutic Potential of HDAC Inhibitors in Neurodegenerative Diseases

Abhay Kumar Singh; Yemgadda Goutham Sudhan; Sudharshanam Lakshmi Chandana; Ashok Iyaswamy; Siva Sundara Kumar Durairajan

doi:10.1007/978-981-95-6099-8_14

Therapeutic Potential of HDAC Inhibitors in Neurodegenerative Diseases

Abhay Kumar Singh
, Yemgadda Goutham Sudhan
, Sudharshanam Lakshmi Chandana
, Ashok Iyaswamy
, Siva Sundara Kumar Durairajan^*

^*Corresponding author for this work

Research output: Chapter in book/report/conference proceeding › Chapter › peer-review

Abstract

Histone deacetylase inhibitors (HDACIs) have emerged as promising therapeutic candidates for neurodegenerative disorders due to their neuroprotective and cognitive-enhancing effects. This chapter examines the potential of HDACIs in Alzheimer’s, Parkinson’s, Huntington’s disease, and amyotrophic lateral sclerosis. Dysregulated HDAC-mediated epigenetic control plays a critical role in disease pathogenesis. HDACIs exert multifaceted actions, including epigenetic modulation, anti-inflammatory, neurotrophic, and antioxidant effects. Preclinical studies demonstrate reduced protein aggregation, attenuated neuroinflammation, and improved synaptic plasticity. Recent advances emphasize isoform-selective HDACIs to minimize offtarget effects. Key challenges include blood–brain barrier penetration, isoform specificity, and dose optimization. Targeted HDACI strategies may help address the multifactorial nature of neurodegenerative diseases.

Original language	English
Title of host publication	Ubiquitin Proteasome System in CNS Neurodegenerative Diseases
Editors	Sarika Singh
Place of Publication	Singapore
Publisher	Springer
Pages	299-327
Number of pages	29
Edition	1st
ISBN (Electronic)	9789819560998
ISBN (Print)	9789819560981, 9789819561018
DOIs	https://doi.org/10.1007/978-981-95-6099-8_14
Publication status	Published - 23 Feb 2026

User-Defined Keywords

Histone deacetylase inhibitors (HDACIs)
Neurodegenerative diseases
Epigenetic modulation
Neuroprotection
Isoform-selective inhibitors
Blood-brain barrier penetration
Alzheimer’s disease
Parkinson’s disease
Huntington’s disease
Neuroinflammation

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10.1007/978-981-95-6099-8_14

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title = "Therapeutic Potential of HDAC Inhibitors in Neurodegenerative Diseases",

abstract = "Histone deacetylase inhibitors (HDACIs) have emerged as promising therapeutic candidates for neurodegenerative disorders due to their neuroprotective and cognitive-enhancing effects. This chapter examines the potential of HDACIs in Alzheimer{\textquoteright}s, Parkinson{\textquoteright}s, Huntington{\textquoteright}s disease, and amyotrophic lateral sclerosis. Dysregulated HDAC-mediated epigenetic control plays a critical role in disease pathogenesis. HDACIs exert multifaceted actions, including epigenetic modulation, anti-inflammatory, neurotrophic, and antioxidant effects. Preclinical studies demonstrate reduced protein aggregation, attenuated neuroinflammation, and improved synaptic plasticity. Recent advances emphasize isoform-selective HDACIs to minimize offtarget effects. Key challenges include blood–brain barrier penetration, isoform specificity, and dose optimization. Targeted HDACI strategies may help address the multifactorial nature of neurodegenerative diseases.",

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Therapeutic Potential of HDAC Inhibitors in Neurodegenerative Diseases. / Singh, Abhay Kumar; Sudhan, Yemgadda Goutham; Chandana, Sudharshanam Lakshmi et al.
Ubiquitin Proteasome System in CNS Neurodegenerative Diseases. ed. / Sarika Singh. 1st. ed. Singapore: Springer, 2026. p. 299-327.

Research output: Chapter in book/report/conference proceeding › Chapter › peer-review

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AU - Durairajan, Siva Sundara Kumar

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Therapeutic Potential of HDAC Inhibitors in Neurodegenerative Diseases

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