Cited by 993Cell death mechanisms and regulationNeuroinflammation and Neurodegeneration MechanismsNF-κB Signaling Pathways

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Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases

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Yuan, Junying, Amin, Palak, Ofengeim, Dimitry·2019·Nature Reviews Neuroscience

DOI 10.1038/s41583-018-0093-1PMC PMC6342007

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Abstract

Apoptosis is crucial for the normal development of the nervous system, whereas neurons in the adult CNS are relatively resistant to this form of cell death. However, under pathological conditions, upregulation of death receptor family ligands, such as tumour necrosis factor (TNF), can sensitize cells in the CNS to apoptosis and a form of regulated necrotic cell death known as necroptosis that is mediated by receptor-interacting protein kinase 1 (RIPK1), RIPK3 and mixed lineage kinase domain-like protein (MLKL). Necroptosis promotes further cell death and neuroinflammation in the pathogenesis of several neurodegenerative diseases, including multiple sclerosis, amyotrophic lateral sclerosis, Parkinson disease and Alzheimer disease. In this Review, we outline the evidence implicating necroptosis in these neurological diseases and suggest that targeting RIPK1 might help to inhibit multiple cell death pathways and ameliorate neuroinflammation. Necroptosis is a form of cell death mediated by receptor-interacting protein kinase 1 (RIPK1), and is observed in several CNS disorders. Here, Yuan, Amin and Ofengeim give an overview of necroptosis in the CNS and explain its relationship with inflammation in CNS disorders.

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Authors: Yuan, J., Amin, P., & Ofengeim, D.
Affiliations: Harvard University (US)
Sanofi (United States) (US)
Corresponding author: Yuan, Junying
ORCID: Yuan, Junying
Amin, Palak
Ofengeim, Dimitry
Venue: Nature Reviews Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2018-11-22
Volume: 20
Issue: 1
Pages: 19-33
ISSN: 1471-003X (ISSN-L)
1471-0048
DOI: 10.1038/s41583-018-0093-1
PMC: PMC6342007
OpenAlex: W2901410206
Semantic Scholar: a6626d511f6ce29e1ffd0f9740b5c693cadb4fb3
Cited by: 967
References: 179
Citations by year: 2026: 110 · 2025: 156 · 2024: 149 · 2023: 152 · 2022: 164 · 2021: 134 · 2020: 65 · 2019: 35
FWCI: 5.80
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature reviews. Neuroscience (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: Denali Therapeutics
National Institutes of Health (4r01ns082257-04)
National Institute on Aging (RF1AG055521, R01AG047231, R21AG059073)
National Institute of Neurological Disorders and Stroke (R01-NS082257)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords: necroptosis, RIPK1, neuroinflammation, RIPK3, MLKL, apoptosis, TNF-α, death receptor ligands, neurodegenerative diseases, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, central nervous system disorders
MeSH terms: Necroptosis, Animals, Brain, Humans, Inflammation, Neurons, Phosphorylation, Neurodegenerative Diseases, Receptor-Interacting Protein Serine-Threonine Kinases

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Necroptosis and RIPK1-mediated neuroinflammation in CNS diseases

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