Cited by 50Genetic Neurodegenerative DiseasesMetabolism, Diabetes, and CancerMitochondrial Function and Pathology

Metformin protects cells from mutant huntingtin toxicity through activation of AMPK and modulation of mitochondrial dynamics

Open access
Jin, Jing, Gu, Hao, Anders, Nicole M., Ren, Tianhua, Jiang, Mali, Tao, Michael, Peng, Qi, Rudek, Michelle A. +1 more·2016·NeuroMolecular Medicine

Abstract

Huntington's disease (HD) is a devastating neurodegenerative disease caused by the pathological elongation of the CAG repeats in the huntingtin gene. Caloric restriction (CR) has been the most reproducible environmental intervention to improve health and prolong life span. We have demonstrated that CR delayed onset and slowed disease progression in a mouse model of HD. Metformin, an antidiabetic drug, mimics CR by acting on cell metabolism at multiple levels. Long-term administration of metformin improved health and life span in mice. In this study, we showed that metformin rescued cells from mutant huntingtin (HTT)-induced toxicity, as indicated by reduced lactate dehydrogenase (LDH) release from cells and preserved ATP levels in cells expressing mutant HTT. Further mechanistic study indicated that metformin activated AMP-activated protein kinase (AMPK) and that inhibition of AMPK activation reduced its protective effects on mutant HTT toxicity, suggesting that AMPK mediates the protection of metformin in HD cells. Furthermore, metformin treatment prevented mitochondrial membrane depolarization and excess fission and modulated the disturbed mitochondrial dynamics in HD cells. We confirmed that metformin crossed the blood-brain barrier after oral administration and activated AMPK in the mouse brain. Our results urge further evaluation of the clinical potential for use of metformin in HD treatment.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1007/s12017-016-8412-z

Cites

30 of 30 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Metformin-dependent AMPK activation protects mitochondria in Huntington's disease by affecting mitochondrial dynamics.

    “metformin-dependent AMPK activation has recently demonstrated protection of mitochondria in huntington's disease by affecting mitochondrial dynamics (Jin et al., 2016).”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

1 retracted

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Jin, J., Gu, H., Anders, N. M., Ren, T., Jiang, M., Tao, M., Peng, Q., Rudek, M. A., & Duan, W.
Affiliations
Johns Hopkins University (US)
Corresponding author
Duan, Wenzhen
Venue
NeuroMolecular Medicine
Published
2016-05-25
Volume
18
Issue
4
Pages
581-592
ISSN
  • 1535-1084 (ISSN-L)
  • 1559-1174
OpenAlex
W2407471740
Cited by
50
References
30
Citations by year
2026: 2 · 2025: 5 · 2024: 2 · 2023: 4 · 2022: 6 · 2021: 7 · 2020: 7 · 2019: 5 · 2018: 7 · 2017: 3 · 2016: 2
FWCI
3.18
Type
journal article
Language
en
Open access
Locations
  • NeuroMolecular Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Neurological Disorders and Stroke (NS082338)
  • National Cancer Institute (CA006973)
  • National Center for Advancing Translational Sciences (TR001079)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
metformin, Huntington's disease, AMPK activation, mitochondrial dynamics, mitochondrial fission, mitochondrial depolarization, blood-brain barrier, neuroprotection, drug repurposing
MeSH terms
Huntingtin Protein, Animals, Disease Models, Animal, Enzyme Activation, Huntington Disease, Metformin, Mitochondria, Neuroprotective Agents, Mice, AMP-Activated Protein Kinases, Mitochondrial Dynamics

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review