Necroptosis in Development and Diseases

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2018 Mar 30

PMID 29593066

Citations 188

Authors

Bing Shan

Heling Pan

Ayaz Najafov

Junying Yuan

Affiliations

Soon will be listed here.

Abstract

Necroptosis, a form of regulated necrotic cell death mediated by RIPK1 (receptor-interacting protein kinase 1) kinase activity, RIPK3, and MLKL (mixed-lineage kinase domain-like pseudokinase), can be activated under apoptosis-deficient conditions. Modulating the activation of RIPK1 by ubiquitination and phosphorylation is critical to control both necroptosis and apoptosis. Mutant mice with kinase-dead RIPK1 or RIPK3 and MLKL deficiency show no detrimental phenotype in regard to development and adult homeostasis. However, necroptosis and apoptosis can be activated in response to various mutations that result in the abortion of the defective embryos and human inflammatory and neurodegenerative pathologies. RIPK1 inhibition represents a key therapeutic strategy for treatment of diseases where blocking both necroptosis and apoptosis can be beneficial.

Citing Articles

RIPK1 in necroptosis and recent progress in related pharmaceutics.

Yao K, Shi Z, Zhao F, Tan C, Zhang Y, Fan H Front Immunol. 2025; 16:1480027.

PMID: 40007541 PMC: 11850271. DOI: 10.3389/fimmu.2025.1480027.

Advances in the Study of Necroptosis in Vascular Dementia: Focus on Blood-Brain Barrier and Neuroinflammation.

Qiu Y, Cheng L, Xiong Y, Liu Z, Shen C, Wang L CNS Neurosci Ther. 2025; 31(2):e70224.

PMID: 39915907 PMC: 11802338. DOI: 10.1111/cns.70224.

RIP kinases and necroptosis in aging and aging-related diseases.

Yang Y, Li X, Zhang T, Xu D Life Med. 2025; 1(1):2-20.

PMID: 39872161 PMC: 11749793. DOI: 10.1093/lifemedi/lnac003.

Receptor-Interacting Protein Kinase-3 Expression Impacts Ocular Vascular Development and Pathological Neovascularization.

Song Y, Wang S, Park S, Hanna B, Johnson K, Darjatmoko S Cells. 2025; 13(24.

PMID: 39768199 PMC: 11726843. DOI: 10.3390/cells13242109.

Harnessing m1A modification: a new frontier in cancer immunotherapy.

Wang X, Ma X, Chen S, Fan M, Jin C, Chen Y Front Immunol. 2024; 15:1517604.

PMID: 39687616 PMC: 11647001. DOI: 10.3389/fimmu.2024.1517604.

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