Cited by 75Histone Deacetylase Inhibitors ResearchAlzheimer's disease research and treatmentsGenetic Neurodegenerative Diseases

The role of altered protein acetylation in neurodegenerative disease

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Kabir, Fariha, Atkinson, Rachel, Cook, Anthony L., Phipps, Andrew James, King, Anna Elizabeth·2023·Frontiers in Aging Neuroscience

Abstract

Acetylation is a key post-translational modification (PTM) involved in the regulation of both histone and non-histone proteins. It controls cellular processes such as DNA transcription, RNA modifications, proteostasis, aging, autophagy, regulation of cytoskeletal structures, and metabolism. Acetylation is essential to maintain neuronal plasticity and therefore essential for memory and learning. Homeostasis of acetylation is maintained through the activities of histone acetyltransferases (HAT) and histone deacetylase (HDAC) enzymes, with alterations to these tightly regulated processes reported in several neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). Both hyperacetylation and hypoacetylation can impair neuronal physiological homeostasis and increase the accumulation of pathophysiological proteins such as tau, α-synuclein, and Huntingtin protein implicated in AD, PD, and HD, respectively. Additionally, dysregulation of acetylation is linked to impaired axonal transport, a key pathological mechanism in ALS. This review article will discuss the physiological roles of protein acetylation and examine the current literature that describes altered protein acetylation in neurodegenerative disorders.

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Crossref · 10.3389/fnagi.2022.1025473

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  • Epigenetic dysregulation through HDACs plays a critical role in synaptic dysfunction and memory loss in Alzheimer's disease.

    “Growing evidence supports that epigenetic dysregulation through histone deacetylases (HDACs) plays a critical role in synaptic dysfunction and memory loss in Alzheimer’s disease”

    From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [8]

    The HDAC enzymes section (page unavailable) says HDAC2 regulates memory formation and synaptic plasticity, and its table lists several HDACs as involved in Alzheimer’s disease. The altered microtubule acetylation section (page unavailable) also links HDAC6 activity to impaired cognition in AD mouse models. These passages do not establish the more specific claim that epigenetic dysregulation through HDACs plays a critical role in both synaptic dysfunction and memory loss in Alzheimer’s disease. (LLM, conf=0.83)

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1 of the 325 references couldn’t be matched to a known paper.

Research works printed but not linked: 4

  1. Chen Y.-A. Lu C.-H. Ke C.-C. Chang C.-W. Yang B.-H. Gelovani J.G.. (eds.) (2020). “Monitoring HDAC4 expression in Alzheimer’s disease using [18 F] TFAHA-PET.” in International Conference of FASMI (FEDERATION OF ASIAN SOCIETIES FOR MOLECULAR IMAGING). Springer.
  2. Le Guen Y. Luo G. Ambati A. Damotte V. Jansen I. Yu E.. (2021). Protective effects of HLA-DRB1* 04 subtypes in Parkinson's and Alzheimer's diseases implicate acetylated tau PHF6 sequences. med Rxiv [Preprint]. doi: 10.1101/2021.12.26.21268354v1 · DOI
  3. Mazzocchi M. (2021). Defining the potential of class-IIa histone deacetylases as a therapeutic target for Parkinson’s disease. PhD Thesis. University College Cork.
  4. Portaleone P. (2004). Encyclopedia of Endocrine Diseases. Milan, Italy: Academic Press, 9– 12.

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Authors
Kabir, F., Atkinson, R., Cook, A. L., Phipps, A. J., & King, A. E.
Affiliations
University of Tasmania (AU)
Corresponding author
Phipps, Andrew James
Venue
Frontiers in Aging Neuroscience
Published
2023-01-04
Volume
14
Pages
1025473-1025473
ISSN
1663-4365 (ISSN-L)
OpenAlex
W4313477105
Cited by
75
References
325
Citations by year
2026: 20 · 2025: 22 · 2024: 25 · 2023: 8
FWCI
1.98
Type
journal article
Language
en
Open access
Locations
  • Frontiers in Aging Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
National Health and Medical Research Council (APP1136913)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
Keywords
protein acetylation, post-translational modification, neurodegenerative diseases, histone acetyltransferase, histone deacetylase, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, tau protein, alpha-synuclein, huntingtin, axonal transport, neuroplasticity

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