RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS

• DOI: 10.1126/science.aaf6803
• Publication Date: 2016-08-04T18:17:52Z
• Authors: Yasushi Ito; Dimitry Ofengeim; Ayaz Najafov; Sudeshna Das; Shahram Saberi; Ying Li; Junichi Hitomi; Hong Zhu; Hongbo Chen; Lior Mayo; Jiefei Geng; Palak Amin; Judy Park DeWitt; Adnan Kasim Mookh...; Marcus Florez; Amanda Tomie Ouchida; Jian-bing Fan; Manolis Pasparakis; Michelle A. Kelliher; John Ravits; Junying Yuan
• Keywords: Optineurin; RIPK1; Degeneration (medical)

Mutations in the optineurin (OPTN) gene have been implicated both familial and sporadic amyotrophic lateral sclerosis (ALS). However, role of this protein central nervous system (CNS) how it may contribute to ALS pathology are unclear. Here, we found that actively suppressed receptor-interacting kinase 1 (RIPK1)-dependent signaling by regulating its turnover. Loss OPTN led progressive dysmyelination axonal degeneration through engagement necroptotic machinery CNS, including RIPK1, RIPK3, mixed lineage domain-like (MLKL). Furthermore, RIPK1- RIPK3-mediated was commonly observed SOD1(G93A) transgenic mice pathological samples from human patients. Thus, RIPK1 RIPK3 play a critical mediating degeneration. inhibiting provide an protective strategy for treatment other degenerative diseases characterized