Cited by 611Amyotrophic Lateral Sclerosis ResearchCell death mechanisms and regulationHereditary Neurological Disorders

RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS

Open access
Ito, Yasushi, Ofengeim, Dimitry, Najafov, Ayaz, Das, Sudeshna, Saberi, Shahram, Li, Ying, Hitomi, Junichi, Zhu, Hong +13 more·2016·Science

Abstract

Axonal pathology and necroptosis in ALS: Necroptosis, a non–caspase-dependent form of cell death, can be reduced in disease states by inhibiting a kinase called RIPK1. Until now, no human mutations have been linked to necroptosis. Ito et al. show that loss of optineurin, which is encoded by a gene that has been implicated in the human neurodegenerative disorder ALS (amyotrophic lateral sclerosis), results in sensitivity to necroptosis and axonal degeneration. When RIPK1-kinase dependent signaling is disrupted in mice that lack optineurin, necroptosis is inhibited and axonal pathology is reversed. Science , this issue p. 603

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 · 10.1126/science.aaf6803

Cites

40 of 40 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?

  • OPTN actively regulates proteasomal turnover of RIPK1, as loss of OPTN induces axonal degeneration via RIPK1-dependent necroptosis.

    “Moreover, it has recently been reported that the autophagic receptor optineurin (OPTN) [509] actively regulates the proteasomal turnover of RIPK1, as the loss of OPTN induces axonal degeneration via RIPK1-dependent necroptosis [510].”

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

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Ito, Y., Ofengeim, D., Najafov, A., Das, S., Saberi, S., Li, Y., Hitomi, J., Zhu, H., Chen, H., Mayo, L., Geng, J., Amin, P., DeWitt, J. P., Mookhtiar, A. K., Florez, M., Ouchida, A. T., Fan, J.-B., Pasparakis, M., Kelliher, M. A., Ravits, J., & Yuan, J.
Affiliations
  • Harvard University (US)
  • Massachusetts General Hospital (US)
  • Brigham and Women's Hospital (US)
  • Illumina (United States) (US)
  • University of Cologne (DE)
  • University of Massachusetts Chan Medical School (US)
Corresponding author
Yuan, Junying
Venue
Science
Published
2016-08-05
Volume
353
Issue
6299
Pages
603-608
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2500850723
Cited by
606
References
40
Citations by year
2026: 43 · 2025: 59 · 2024: 66 · 2023: 74 · 2022: 58 · 2021: 79 · 2020: 74 · 2019: 57 · 2018: 55 · 2017: 33 · 2016: 6 · 2012: 1
FWCI
38.10
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institute of Neurological Disorders and Stroke (1R01NS082257)
  • National Institute on Aging (1R01AG047231)
  • NIH
  • National Science and Technology Major Project of China (2014ZX09102001-002)
  • State Key Program of National Natural Science of China (31530041)
  • National Institute of Allergy and Infectious Diseases (2RO1AI075118)
  • European Research Council (323040)
  • Daiichi Sankyo Foundation of Life Science
  • The Nakatomi Foundation
  • Mochida Memorial Foundation for Medical and Pharmaceutical Research
  • Japan Society for the Promotion of Science
  • National Multiple Sclerosis Society
  • National Multiple Sclerosis Society Career Transition Award
  • Huazhong University of Science and Technology
Topics
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
Keywords
amyotrophic lateral sclerosis, optineurin, RIPK1, RIPK3, MLKL, necroptosis, axonal degeneration, neuroinflammation, dysmyelination, SOD1 G93A mice, axonal protection
MeSH terms
Superoxide Dismutase-1, Amyotrophic Lateral Sclerosis, Animals, Axons, Humans, Inflammation, Mice, Transgenic, Necrosis, Nerve Degeneration, Spinal Cord, Superoxide Dismutase, Suppression, Genetic, Apoptosis, Cell Cycle Proteins, Membrane Transport Proteins, Transcription Factor TFIIIA, Mice, Receptor-Interacting Protein Serine-Threonine Kinases

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