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Published on: December 19, 2017
Targeting Necroptosis: A Novel Therapeutic Option for Retinal Degenerative Diseases
Qi Zhang1,2, Xi-Min Hu1, Wen-Juan Zhao1
1Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, China.
Abstract:
The discovery of the necroptosis, a form of regulated necrosis that is mediated by receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed-lineage kinase domain-like pseudokinase (MLKL), represents a major breakthrough that has dramatically altered the conception of necrosis - traditionally thought of as uncontrolled cell death - in various human diseases. Retinal cell death is a leading cause of blindness and has been identified in most retinal diseases, e.g., age-related macular degeneration, glaucoma, retinal detachment, retinitis pigmentosa, etc. Increasing evidence demonstrates that retinal degenerative diseases also share a common mechanism in necroptosis. Exacerbated necroptotic cell death hinders the treatment for retinal degenerative diseases. In this review, we highlight recent advances in identifying retinal necroptosis, summarize the underlying mechanisms of necroptosis in retinal degenerative diseases, and discuss potential anti-necroptosis strategies, such as selective inhibitors and chemical agents, for treating retinal degenerative diseases.
Insights
Necroptosis, a regulated cell death pathway involving RIPK1, RIPK3, and MLKL, is implicated in retinal diseases causing blindness. Targeting necroptosis offers new therapeutic strategies for these conditions.
Area of Science:
- Cell Biology
- Ophthalmology
- Pathology
Background:
- Necroptosis is a regulated form of necrosis mediated by RIPK1, RIPK3, and MLKL.
- Retinal cell death is a primary cause of blindness and is implicated in numerous retinal diseases.
- Growing evidence links necroptosis to the mechanisms underlying retinal degenerative diseases.
Purpose of the Study:
- To review recent advancements in identifying necroptosis in retinal diseases.
- To summarize the molecular mechanisms of necroptosis in the context of retinal degeneration.
- To discuss potential therapeutic strategies targeting necroptosis for treating retinal diseases.
Main Methods:
- Literature review of studies on necroptosis and retinal diseases.
- Analysis of molecular pathways involved in necroptosis.
- Evaluation of potential anti-necroptosis therapeutic agents.
Main Results:
- Necroptosis is a common mechanism in various retinal degenerative diseases.
- Dysregulated necroptosis exacerbates retinal cell death, hindering treatment efficacy.
- Selective inhibitors and chemical agents show promise in combating necroptosis.
Conclusions:
- Necroptosis plays a significant role in the pathogenesis of retinal degenerative diseases.
- Targeting necroptosis presents a promising avenue for developing novel treatments for blindness-causing retinal conditions.
