Evidence map›Paper›PMID 37919281›Full record

ArticleNature communications2023

A neurodegeneration checkpoint mediated by REST protects against the onset of Alzheimer's disease.

Liviu Aron, Chenxi Qiu, Zhen Kai Ngian, Marianna Liang, Derek Drake, Jaejoon Choi, Marty A Fernandez, Perle Roche, Emma L Bunting, Ella K Lacey and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.2field-weighted citation impact, top 12% of its field
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

13 citing papers in PubMed, 14 citations in OpenAlex.

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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

16 authors at 4 institutions in 1 country.

Liviu Aron *Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA.
Chenxi Qiu *Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA.
Zhen Kai NgianDepartment of Genetics, Harvard Medical School, Boston, MA, 02115, USA.
Marianna LiangDepartment of Genetics, Harvard Medical School, Boston, MA, 02115, USA.
Derek DrakeDepartment of Genetics, Harvard Medical School, Boston, MA, 02115, USA.
Jaejoon ChoiDepartment of Genetics, Harvard Medical School, Boston, MA, 02115, USA.
Marty A FernandezCenter for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Perle RocheDepartment of Genetics, Harvard Medical School, Boston, MA, 02115, USA.
Emma L BuntingDepartment of Genetics, Harvard Medical School, Boston, MA, 02115, USA.
Ella K LaceyDepartment of Genetics, Harvard Medical School, Boston, MA, 02115, USA.ORCID 0009-0003-3863-5554
Sara E HamplovaDepartment of Genetics, Harvard Medical School, Boston, MA, 02115, USA.
Monlan YuanDepartment of Genetics, Harvard Medical School, Boston, MA, 02115, USA.
Michael S WolfeCenter for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA, 02115, USA.ORCID 0000-0002-5721-9092
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL60612, USA.
Eunjung A LeeDivision of Genetics and Genomics, Boston Children's Hospital, Boston, MA, 02115, USA.
Bruce A YanknerDepartment of Genetics, Harvard Medical School, Boston, MA, 02115, USA. bruce_yankner@hms.harvard.edu.ORCID 0009-0008-8982-225X
Harvard University · USBrigham and Women's Hospital · USBoston Children's Hospital · USRush University Medical Center · US

Funding

SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI ARFANAKIS, KONSTANTINOS · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
RISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4M
Multi-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targetsU01AG061356 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2018 to 2022
$13.7M
Targeting a Novel Regulator of Brain Aging and Alzheimer's Disease (ADMINISTRATIVE SUPPLEMENT- SAGE)R01AG046174 · NIA · HARVARD MEDICAL SCHOOL · PI TSAI, LI-HUEI, YANKNER, BRUCE A · 2014 to 2018
$4.9M
Exploring a Novel Paradigm of Schizophrenia and Bipolar DisorderR01MH113279 · NIMH · HARVARD MEDICAL SCHOOL · PI CHURCH, GEORGE M, YANKNER, BRUCE A · 2016 to 2020
$4.7M
Targeting REST in Alzheimer's DiseaseR01AG069042 · NIA · HARVARD MEDICAL SCHOOL · PI YANKNER, BRUCE A · 2021 to 2025
$4.5M
Structure and Function of Gamma-Secretase in Familial Alzheimer's DiseaseR01AG066986 · NIA · UNIVERSITY OF KANSAS LAWRENCE · PI Yinglong Miao, Michael S Wolfe · 2020 to 2026
$3.6M
Mechanism for endogenous retroelements to mimic ancient exogenous identities in aging and diseased human tissueDP2AG072437 · NIA · BOSTON CHILDREN'S HOSPITAL · PI LEE, EUNJUNG ALICE · 2020 to 2020
$2.7M
Modeling the Aging EpigenomeDP1OD006849 · OD · HARVARD MEDICAL SCHOOL · PI YANKNER, BRUCE A · 2010 to 2011
$1.7M
The role of somatic mutation in neurodegenerative diseaseK01AG051791 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI LEE, EUNJUNG ALICE · 2016 to 2020
$655k
NIA NIH HHS DP2 AG072437NIA NIH HHS K01 AG051791NIA NIH HHS P30 AG010161NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG046174NIA NIH HHS R01 AG066986NIA NIH HHS R01 AG069042NIA NIH HHS U01 AG061356NIH HHS DP1 OD006849NIMH NIH HHS R01 MH113279
6 · The paper itself

Abstract

Many aging individuals accumulate the pathology of Alzheimer's disease (AD) without evidence of cognitive decline. Here we describe an integrated neurodegeneration checkpoint response to early pathological changes that restricts further disease progression and preserves cognitive function. Checkpoint activation is mediated by the REST transcriptional repressor, which is induced in cognitively-intact aging humans and AD mouse models at the onset of amyloid β-protein (Aβ) deposition and tau accumulation. REST induction is mediated by the unfolded protein response together with β-catenin signaling. A consequence of this response is the targeting of REST to genes involved in key pathogenic pathways, resulting in downregulation of gamma secretase, tau kinases, and pro-apoptotic proteins. Deletion of REST in the 3xTg and J20 AD mouse models accelerates Aβ deposition and the accumulation of misfolded and phosphorylated tau, leading to neurodegeneration and cognitive decline. Conversely, viral-mediated overexpression of REST in the hippocampus suppresses Aβ and tau pathology. Thus, REST mediates a neurodegeneration checkpoint response with multiple molecular targets that may protect against the onset of AD.

Indexed as

Alzheimer DiseaseCognitive DysfunctionAgingAmyloid beta-PeptidesAnimalsDisease Models, AnimalHumansMiceMice, TransgenicRE1-Silencing Transcription Factortau ProteinsAmyloid beta-PeptidesRE1-Silencing Transcription Factortau Proteins

Identifiers

PMID37919281
PMCPMC10622455
OpenAlexW4388212583

What OpenQuestion holds

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LicenceCC BY
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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 OpenQuestion graph.