Evidence map›Paper›PMID 28355558›Full record

ArticleCell reports2017

Neuroprotective Functions for the Histone Deacetylase SIRT6.

Shai Kaluski, Miguel Portillo, Antoine Besnard, Daniel Stein, Monica Einav, Lei Zhong, Uwe Ueberham, Thomas Arendt, Raul Mostoslavsky, Amar Sahay and 1 more

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

Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 1 pooled it
9.1field-weighted citation impact, top 1% 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

88 citing papers in PubMed, 1 synthesis or guideline pooled it, 161 citations in OpenAlex.

  1. Pooled it
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  8. Review
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  12. Structural and enzymatic plasticity of SIRT6 deacylase activity.The Journal of biological chemistry · 2025
    Article
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28 more citing papers are in PubMed but not listed here.

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

11 authors at 4 institutions in 3 countries.

Shai KaluskiDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Miguel PortilloDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Antoine BesnardThe Massachusetts General Hospital Cancer Center and The MGH Center for Regenerative Medicine, Harvard Medical School, Boston, MA 02114, USA; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Daniel SteinDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Monica EinavDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Lei ZhongThe Massachusetts General Hospital Cancer Center and The MGH Center for Regenerative Medicine, Harvard Medical School, Boston, MA 02114, USA; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Uwe UeberhamPaul Flechsig Institute for Brain Research, University of Leipzig, Liebigstrasse 19, 04103 Leipzig, Germany.
Thomas ArendtPaul Flechsig Institute for Brain Research, University of Leipzig, Liebigstrasse 19, 04103 Leipzig, Germany.
Raul MostoslavskyThe Massachusetts General Hospital Cancer Center and The MGH Center for Regenerative Medicine, Harvard Medical School, Boston, MA 02114, USA; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Amar SahayThe Massachusetts General Hospital Cancer Center and The MGH Center for Regenerative Medicine, Harvard Medical School, Boston, MA 02114, USA; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Debra ToiberDepartment of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel. Electronic address: toiber@bgu.ac.il.
Ben-Gurion University of the Negev · ILBroad Institute · USLeipzig University · DEMassachusetts General Hospital · US

Funding

Molecular control of excitation-inhibition balance to encode ambiguous threatsR01MH104175 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI SAHAY, AMAR · 2014 to 2018
$2.7M
The Role of SIRT6 and Metabolism in APC Mediated TumorigenesisR01CA175727 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI MOSTOSLAVSKY, GUSTAVO, MOSTOSLAVSKY, RAUL · 2014 to 2018
$2.6M
Re-engineering excitation-inhibition connectivity to rejuvenate memory circuits in agingRF1AG048908 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI SAHAY, AMAR · 2016 to 2016
$2.0M
NCI NIH HHS R01 CA175727NIA NIH HHS RF1 AG048908NIMH NIH HHS R01 MH104175
6 · The paper itself

Abstract

The histone deacetylase SIRT6 promotes DNA repair, but its activity declines with age with a concomitant accumulation of DNA damage. Furthermore, SIRT6 knockout mice exhibit an accelerated aging phenotype and die prematurely. Here, we report that brain-specific SIRT6-deficient mice survive but present behavioral defects with major learning impairments by 4 months of age. Moreover, the brains of these mice show increased signs of DNA damage, cell death, and hyperphosphorylated Tau-a critical mark in several neurodegenerative diseases. Mechanistically, SIRT6 regulates Tau protein stability and phosphorylation through increased activation of the kinase GSK3α/β. Finally, SIRT6 mRNA and protein levels are reduced in patients with Alzheimer's disease. Taken together, our results suggest that SIRT6 is critical to maintain genomic stability in the brain and that its loss leads to toxic Tau stability and phosphorylation. Therefore, SIRT6 and its downstream signaling could be targeted in Alzheimer's disease and age-related neurodegeneration.

Indexed as

NeuroprotectionAlzheimer DiseaseAnimalsApoptosisAtaxia Telangiectasia Mutated ProteinsBrainDNA DamageEnzyme ActivationGene DeletionGenomic InstabilityGlycogen Synthase Kinase 3HumansLearningMice, Inbred C57BLMice, KnockoutOrgan SpecificityAtaxia Telangiectasia Mutated ProteinsGlycogen Synthase Kinase 3SIRT6 protein, humanSirt6 protein, mouseSirtuinstau ProteinsagingAlzheimer’s diseaseDNA damageGSK3SIRT6Tau

Identifiers

PMID28355558
PMCPMC5389893
OpenAlexW2602238152

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.