Ito, Yasushi, Ofengeim, Dimitry, Najafov, Ayaz ORCID: 0000-0002-1350-2056, Das, Sudeshna ORCID: 0000-0002-9486-6811, Saberi, Shahram, Li, Ying, Hitomi, Junichi, Zhu, Hong ORCID: 0000-0002-2575-4031, Chen, Hongbo ORCID: 0000-0002-9084-7277, Mayo, Lior ORCID: 0000-0002-1296-6692, Geng, Jiefei, Amin, Palak ORCID: 0000-0001-5617-8703, DeWitt, Judy Park, Mookhtiar, Adnan Kasim, Florez, Marcus, Ouchida, Amanda Tomie, Fan, Jian-bing, Pasparakis, Manolis ORCID: 0000-0002-9870-0966, Kelliher, Michelle A., Ravits, John and Yuan, Junying (2016). RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS. Science, 353 (6299). S. 603 - 609. WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 1095-9203

Full text not available from this repository.

Abstract

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

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Ito, YasushiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ofengeim, DimitryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Najafov, AyazUNSPECIFIEDorcid.org/0000-0002-1350-2056UNSPECIFIED
Das, SudeshnaUNSPECIFIEDorcid.org/0000-0002-9486-6811UNSPECIFIED
Saberi, ShahramUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, YingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hitomi, JunichiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhu, HongUNSPECIFIEDorcid.org/0000-0002-2575-4031UNSPECIFIED
Chen, HongboUNSPECIFIEDorcid.org/0000-0002-9084-7277UNSPECIFIED
Mayo, LiorUNSPECIFIEDorcid.org/0000-0002-1296-6692UNSPECIFIED
Geng, JiefeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Amin, PalakUNSPECIFIEDorcid.org/0000-0001-5617-8703UNSPECIFIED
DeWitt, Judy ParkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mookhtiar, Adnan KasimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Florez, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ouchida, Amanda TomieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fan, Jian-bingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pasparakis, ManolisUNSPECIFIEDorcid.org/0000-0002-9870-0966UNSPECIFIED
Kelliher, Michelle A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ravits, JohnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yuan, JunyingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-266788
DOI: 10.1126/science.aaf6803
Journal or Publication Title: Science
Volume: 353
Number: 6299
Page Range: S. 603 - 609
Date: 2016
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication: WASHINGTON
ISSN: 1095-9203
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
AMYOTROPHIC-LATERAL-SCLEROSIS; KAPPA-B ACTIVATION; MOTOR-NEURON DEATH; CELL-DEATH; SELF-DESTRUCTION; OPTINEURIN; KINASE; IDENTIFICATION; MICE; REGENERATIONMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/26678

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item