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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Additional file 3 of Hyperphosphorylated tau mediates neuronal death by inducing necroptosis and inflammation in Alzheimer’s disease
Dong, Y., Yu, H., Li, X., Bian, K., Zheng, Y., Dai, M., Feng, X., Sun, Y., He, Y., Yu, B., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20495836
Additional file 7 of Microglia and macrophage exhibit attenuated inflammatory response and ferroptosis resistance after RSL3 stimulation via increasing Nrf2 expression
Cui, Y., Zhang, Z., Zhou, X., Zhao, Z., Zhao, R., Xu, X., Kong, X., Ren, J., Yao, X., Wen, Q., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16909791
Additional file 7 of Hyperphosphorylated tau mediates neuronal death by inducing necroptosis and inflammation in Alzheimer’s disease
Dong, Y., Yu, H., Li, X., Bian, K., Zheng, Y., Dai, M., Feng, X., Sun, Y., He, Y., Yu, B., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20495851
Additional file 8 of TNF-mediated neuroinflammation is linked to neuronal necroptosis in Alzheimer's disease hippocampus
Jayaraman, A., Htike, T. T., James, R., Picón, C., & Reynolds, R. (2021) · Figshare · doi:10.6084/m9.figshare.16778490
Additional file 3 of Transcriptome analysis of long non-coding RNA and mRNA Profiles in VSV-infected BHK-21 Cells
Han, W., Fei, X., Yang, F., Sun, X., Yang, J., Qiu, J., Zhang, L., Zhang, W., Chen, G., Han, W., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26667879
Additional file 4 of Transcriptome analysis of long non-coding RNA and mRNA Profiles in VSV-infected BHK-21 Cells
Han, W., Fei, X., Yang, F., Sun, X., Yang, J., Qiu, J., Zhang, L., Zhang, W., Chen, G., Han, W., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26667882
Additional file 1 of MLKL deficiency alleviates neuroinflammation and motor deficits in the α-synuclein transgenic mouse model of Parkinson’s disease
Geng, L., Gao, W., Saiyin, H., Li, Y., Zeng, Y., Zhang, Z., Li, X., Liu, Z., Gao, Q., An, P., et al. (2023) · Figshare · doi:10.6084/m9.figshare.24715471
Additional file 14 of Alternative splicing coupled to nonsense-mediated decay coordinates downregulation of non-neuronal genes in developing mouse neurons
Zhuravskaya, A., Yap, K., Hamid, F., & Makeyev, E. V. (2024) · Figshare · doi:10.6084/m9.figshare.26736747
Additional file 5 of Transcriptome analysis of long non-coding RNA and mRNA Profiles in VSV-infected BHK-21 Cells
Han, W., Fei, X., Yang, F., Sun, X., Yang, J., Qiu, J., Zhang, L., Zhang, W., Chen, G., Han, W., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26667885
Additional file 1 of Dopamine enhances recovery after traumatic brain injury through ubiquitylation and autophagic degradation of RIPK1
Luo, H., Liu, N., & Lin, C. (2024) · Figshare · doi:10.6084/m9.figshare.25248899
Additional file 2 of RIPK1 polymorphisms and expression levels: impact on genetic susceptibility and clinical outcome of epithelial ovarian cancer
Wang, X., Deng, K., Tao, J., Zou, J., Du, Y., & Dai, L. (2024) · Figshare · doi:10.6084/m9.figshare.24630466
Additional file 5 of Hyperphosphorylated tau mediates neuronal death by inducing necroptosis and inflammation in Alzheimer’s disease
Dong, Y., Yu, H., Li, X., Bian, K., Zheng, Y., Dai, M., Feng, X., Sun, Y., He, Y., Yu, B., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20495842
Additional file 4 of Alternative splicing coupled to nonsense-mediated decay coordinates downregulation of non-neuronal genes in developing mouse neurons
Zhuravskaya, A., Yap, K., Hamid, F., & Makeyev, E. V. (2024) · Figshare · doi:10.6084/m9.figshare.26736717
Additional file 9 of Alternative splicing coupled to nonsense-mediated decay coordinates downregulation of non-neuronal genes in developing mouse neurons
Zhuravskaya, A., Yap, K., Hamid, F., & Makeyev, E. V. (2024) · Figshare · doi:10.6084/m9.figshare.26736732
Additional file 5 of Microglia and macrophage exhibit attenuated inflammatory response and ferroptosis resistance after RSL3 stimulation via increasing Nrf2 expression
Cui, Y., Zhang, Z., Zhou, X., Zhao, Z., Zhao, R., Xu, X., Kong, X., Ren, J., Yao, X., Wen, Q., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16909785
Additional file 4 of Microglia and macrophage exhibit attenuated inflammatory response and ferroptosis resistance after RSL3 stimulation via increasing Nrf2 expression
Cui, Y., Zhang, Z., Zhou, X., Zhao, Z., Zhao, R., Xu, X., Kong, X., Ren, J., Yao, X., Wen, Q., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16909782
Additional file 7 of Alternative splicing coupled to nonsense-mediated decay coordinates downregulation of non-neuronal genes in developing mouse neurons
Zhuravskaya, A., Yap, K., Hamid, F., & Makeyev, E. V. (2024) · Figshare · doi:10.6084/m9.figshare.26736726
Additional file 1 of RIPK3 activation induces TRIM28 derepression in cancer cells and enhances the anti-tumor microenvironment
Park, H.-H., Kim, H.-R., Park, S.-Y., Hwang, S.-M., Hong, S. M., Park, S., Kang, H. C., Morgan, M. J., Cha, J.-H., Lee, D., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16305850
Additional file 2 of Transcriptome analysis of long non-coding RNA and mRNA Profiles in VSV-infected BHK-21 Cells
Han, W., Fei, X., Yang, F., Sun, X., Yang, J., Qiu, J., Zhang, L., Zhang, W., Chen, G., Han, W., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25001743
Additional file 2 of Hyperphosphorylated tau mediates neuronal death by inducing necroptosis and inflammation in Alzheimer’s disease
Dong, Y., Yu, H., Li, X., Bian, K., Zheng, Y., Dai, M., Feng, X., Sun, Y., He, Y., Yu, B., et al. (2022) · Figshare · doi:10.6084/m9.figshare.20495833
Additional file 3 of RIPK1 polymorphisms and expression levels: impact on genetic susceptibility and clinical outcome of epithelial ovarian cancer
Wang, X., Deng, K., Tao, J., Zou, J., Du, Y., & Dai, L. (2024) · Figshare · doi:10.6084/m9.figshare.26644468
Additional file 8 of Alternative splicing coupled to nonsense-mediated decay coordinates downregulation of non-neuronal genes in developing mouse neurons
Zhuravskaya, A., Yap, K., Hamid, F., & Makeyev, E. V. (2024) · Figshare · doi:10.6084/m9.figshare.26736729
Additional file 10 of Alternative splicing coupled to nonsense-mediated decay coordinates downregulation of non-neuronal genes in developing mouse neurons
Zhuravskaya, A., Yap, K., Hamid, F., & Makeyev, E. V. (2024) · Figshare · doi:10.6084/m9.figshare.26736735
Additional file 2 of Microglia and macrophage exhibit attenuated inflammatory response and ferroptosis resistance after RSL3 stimulation via increasing Nrf2 expression
Cui, Y., Zhang, Z., Zhou, X., Zhao, Z., Zhao, R., Xu, X., Kong, X., Ren, J., Yao, X., Wen, Q., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16909776
Additional file 1 of A necroptosis-related gene signature to predict prognosis and immune features in hepatocellular carcinoma
Zhang, K., Li, J., & 袁恩武 (2023) · Figshare · doi:10.6084/m9.figshare.23689724
Additional file 3 of Microglia and macrophage exhibit attenuated inflammatory response and ferroptosis resistance after RSL3 stimulation via increasing Nrf2 expression
Cui, Y., Zhang, Z., Zhou, X., Zhao, Z., Zhao, R., Xu, X., Kong, X., Ren, J., Yao, X., Wen, Q., et al. (2021) · Figshare · doi:10.6084/m9.figshare.16909779
Additional file 6 of Alternative splicing coupled to nonsense-mediated decay coordinates downregulation of non-neuronal genes in developing mouse neurons
Zhuravskaya, A., Yap, K., Hamid, F., & Makeyev, E. V. (2024) · Figshare · doi:10.6084/m9.figshare.26736723

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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