Evidence map›Paper›PMID 40817058›Full record

ArticleBMC biology2025

CoREST3 exhibits isoform specific expression in Alzheimer's disease and regulation of HDAC2.

Simon Maksour, Helena Targa Dias Anastacio, Jeremy S Lum, Samara Walpole, Kelly A Newell, Calista Turner, Adile Kaban, Rachelle Balez, Julia Lim, Greg T Sutherland and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Simon MaksourSchool of Medical, Indigenous and Health Science and Molecular Horizons, University of Wollongong, Northfields Avenue, Wollongong, NSW, 2522, Australia. smaksour@uow.edu.au.
Helena Targa Dias AnastacioSchool of Medical, Indigenous and Health Science and Molecular Horizons, University of Wollongong, Northfields Avenue, Wollongong, NSW, 2522, Australia.
Jeremy S LumSchool of Medical, Indigenous and Health Science and Molecular Horizons, University of Wollongong, Northfields Avenue, Wollongong, NSW, 2522, Australia.
Samara WalpoleSchool of Medical, Indigenous and Health Science and Molecular Horizons, University of Wollongong, Northfields Avenue, Wollongong, NSW, 2522, Australia.
Kelly A NewellSchool of Medical, Indigenous and Health Science and Molecular Horizons, University of Wollongong, Northfields Avenue, Wollongong, NSW, 2522, Australia.
Calista TurnerSchool of Chemistry and Molecular Bioscience and Molecular Horizons, University of Wollongong, Northfields Avenue, Wollongong, NSW, 2522, Australia.
Adile KabanSchool of Chemistry and Molecular Bioscience and Molecular Horizons, University of Wollongong, Northfields Avenue, Wollongong, NSW, 2522, Australia.
Rachelle BalezSchool of Chemistry and Molecular Bioscience and Molecular Horizons, University of Wollongong, Northfields Avenue, Wollongong, NSW, 2522, Australia.
Julia LimSchool of Medical Sciences and, Faculty of Medicine and Health, Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia.
Greg T SutherlandSchool of Medical Sciences and, Faculty of Medicine and Health, Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia.
Lezanne Ooi *School of Chemistry and Molecular Bioscience and Molecular Horizons, University of Wollongong, Northfields Avenue, Wollongong, NSW, 2522, Australia. lezanne@uow.edu.au.
Mirella Dottori *School of Medical, Indigenous and Health Science and Molecular Horizons, University of Wollongong, Northfields Avenue, Wollongong, NSW, 2522, Australia. mdottori@uow.edu.au.

Funding

Brain Tissue Resource Centre for Alcohol ResearchR28AA012725 · NIAAA · UNIVERSITY OF SYDNEY · PI Greg Trevor Sutherland · 2012 to 2026
$7.0M
NIAAA NIH HHS R28 AA012725
6 · The paper itself

Abstract

backgroundThe epigenetic regulator, histone deacetylase 2 (HDAC2), is dysregulated in Alzheimer's disease (AD), resulting in disruption to neuronal dynamics, memory and cognition. The transcriptional repressor, REST corepressor 3 (CoREST3) has a potential binding site upstream of Hdac2 and therefore we hypothesised CoREST3 would directly regulate HDAC2 and that CoREST3 expression would be altered in the AD brain.

resultsCoREST3 exhibited three distinct bands at ~ 70 kDa (band I), ~ 60 kDa (band II) and ~ 55 kDa (band III), which were consistent with CoREST3, as shRNA mediated knockdown reduced levels of all three bands. CoREST3 protein levels (band II) in AD post mortem brain tissue were significantly decreased in the superior temporal gyrus (STG), inferior temporal gyrus (ITG) and precuneus (PRE), whereas CoREST3 Band III was significantly increased in the PRE and primary visual cortex (PVC). Additionally, HDAC2 was significantly decreased by > 50% in the STG, PRE and PVC. CoREST3 bound upstream of the transcription start site of HDAC2 in induced pluripotent stem cell (iPSC)-derived cortical neurons, and gene knockdown of CoREST3 resulted in a significant increase in HDAC2 expression (p < 0.01). Through the overexpression of each of the six CoREST3 isoforms we demonstrated that Band I represents isoform A and isoform E, Band II is likely a combination of isoform B and isoform C and Band III is isoform D and isoform F. The overexpression of CoREST3 isoform A (RCOR3-variant 1 led to a significant twofold increase in HDAC2 protein levels in cortical neurons (p < 0.05), conversely CoREST3 isoform F overexpression resulted in the opposite effect, reducing HDAC2 levels by 48% (p < 0.05).

conclusionsTogether these data suggest that CoREST3 plays an isoform specific and direct role in repressing HDAC2, with dysregulated CoREST3 expression in AD possibly contributing to altered HDAC2 levels involved in AD pathogenesis.

Indexed as

Alzheimer DiseaseCo-Repressor ProteinsGene Expression RegulationHistone Deacetylase 2Nerve Tissue ProteinsAgedBrainFemaleHumansMaleNeuronsProtein IsoformsRepressor ProteinsCo-Repressor ProteinsHDAC2 protein, humanHistone Deacetylase 2Nerve Tissue ProteinsProtein IsoformsRepressor ProteinsAlzheimer’s diseaseCoREST3HDAC2IPSCNeuronsRCOR3

Identifiers

PMID40817058
PMCPMC12357483

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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.