Evidence map›Paper›PMID 26677765›Full record

ArticleStem cell reports2015

Metformin Acts on Two Different Molecular Pathways to Enhance Adult Neural Precursor Proliferation/Self-Renewal and Differentiation.

Michael Fatt, Karolynn Hsu, Ling He, Fredric Wondisford, Freda D Miller, David R Kaplan, Jing Wang

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

Article in Stem cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

62 citing papers in PubMed, 138 citations in OpenAlex.

  1. Article
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  3. Hallmarks of stem cell aging.Cell stem cell · 2025
    Review
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2 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

7 authors at 5 institutions in 2 countries.

Michael FattProgram in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5G 1X5, Canada.
Karolynn HsuRegenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada.
Ling HeDepartment of Pediatrics and Medicine, Johns Hopkins Medical School, Baltimore, MD 21287, USA.
Fredric WondisfordDepartment of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
Freda D MillerProgram in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1X5, Canada; Department of Physiology, University of Toronto, Toronto, ON M5G 1X5, Canada.
David R KaplanProgram in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1X5, Canada.
Jing WangRegenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada; Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Brain and Mind Research Institute, University of Ottawa, Ottawa, ON K1H 8M5, Canada. Electronic address: jiwang@ohri.ca.
Hospital for Sick Children · CAOttawa Hospital · CAJohns Hopkins University · USJohnson University · USUniversity of Toronto · CA

Funding

Transcriptional coactivators and hepatic glucose productionR01DK063349 · NIDDK · UNIVERSITY OF CHICAGO · PI WONDISFORD, FREDRIC E. · 2002 to 2017
$5.0M
NIDDK NIH HHS R01 DK063349
6 · The paper itself

Abstract

The recruitment of endogenous adult neural stem cells for brain repair is a promising regenerative therapeutic strategy. This strategy involves stimulation of multiple stages of adult neural stem cell development, including proliferation, self-renewal, and differentiation. Currently, there is a lack of a single therapeutic approach that can act on these multiple stages of adult neural stem cell development to enhance neural regeneration. Here we show that metformin, an FDA-approved diabetes drug, promotes proliferation, self-renewal, and differentiation of adult neural precursors (NPCs). Specifically, we show that metformin enhances adult NPC proliferation and self-renewal dependent upon the p53 family member and transcription factor TAp73, while it promotes neuronal differentiation of these cells by activating the AMPK-aPKC-CBP pathway. Thus, metformin represents an optimal candidate neuro-regenerative agent that is capable of not only expanding the adult NPC population but also subsequently driving them toward neuronal differentiation by activating two distinct molecular pathways.

Indexed as

Adult Stem CellsAMP-Activated Protein KinasesAnimalsCell ProliferationCells, CulturedCREB-Binding ProteinDNA-Binding ProteinsHumansHypoglycemic AgentsMetforminMiceNeural Stem CellsNeurogenesisNuclear ProteinsProtein Kinase CSignal TransductionAMP-Activated Protein KinasesCREB-Binding ProteinCrebbp protein, mouseDNA-Binding ProteinsHypoglycemic AgentsMetforminNuclear ProteinsPKC-3 proteinProtein Kinase CTrp73 protein, mouseTumor Protein p73Tumor Suppressor Proteins

Identifiers

PMID26677765
PMCPMC4682208
OpenAlexW2173802285

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.