Title：RIPK1mediatesaxonaldegenerationbypromotinginflammationandnecroptosisinALS.

Author：ItoY,OfengeimD,NajafovAetal.

Science.Aug5;():-8.

Abstract

Mutationsintheoptineurin(OPTN)genehavebeenimplicatedinbothfamilialandsporadicamyotrophiclateralsclerosis(ALS).However,theroleofthisproteininthecentralnervoussystem(CNS)andhowitmaycontributetoALSpathologyareunclear.Here,wefoundthatoptineurinactivelysuppressedreceptor-interactingkinase1(RIPK1)-dependentsignalingbyregulatingitsturnover.LossofOPTNledtoprogressivedysmyelinationandaxonaldegenerationthroughengagementofnecroptoticmachineryintheCNS,includingRIPK1,RIPK3,andmixedlineagekinasedomain-likeprotein(MLKL).Furthermore,RIPK1-andRIPK3-mediatedaxonalpathologywas







































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