Axonal Degeneration: RIPK1 Multitasking in ALS
| Autor: | Serge Przedborski, Kristin A. Politi |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Necroptosis Apoptosis Inflammation Biology Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences RIPK1 0302 clinical medicine medicine Humans Human multitasking Amyotrophic lateral sclerosis Microglia Kinase Amyotrophic Lateral Sclerosis Neurodegenerative Diseases medicine.disease 030104 developmental biology medicine.anatomical_structure Receptor-Interacting Protein Serine-Threonine Kinases Immunology medicine.symptom General Agricultural and Biological Sciences Axonal degeneration Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Current Biology. 26:R932-R934 |
| ISSN: | 0960-9822 |
| Popis: | Mutations in Optineurin (Optn) gene have been implicated in both familial and sporadic amyotrophic lateral sclerosis (ALS). However, the role of this protein in the central nervous system (CNS) and how it may contribute to ALS pathology is unclear. Here, we found that optineurin actively suppressed RIPK1-dependent signaling by regulating its turnover. Loss-of-OPTN led to progressive dysmyelination and axonal degeneration through engagement of necroptotic machinery, including RIPK1, RIPK3 and MLKL, in the CNS. Furthermore, RIPK1/RIPK3-mediated axonal pathology was commonly observed in SOD1G93A transgenic mice and pathological samples from human ALS. Thus, RIPK1/RIPK3 plays a critical role in mediating progressive axonal degeneration and inhibiting RIPK1 kinase may provide an axonal protective strategy for the treatment of ALS and other human degenerative diseases characterized by axonal degeneration. |
| Databáze: | OpenAIRE |
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