RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS-Reference-Cited by-同舟云学术

RIPK1 mediates axonal degeneration by promoting inflammation and necroptosis in ALS

Published:2016-08-05 Issue:6299 Volume:353 Page:603-608
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Ito Yasushi¹,Ofengeim Dimitry¹,Najafov Ayaz¹,Das Sudeshna²,Saberi Shahram³⁴,Li Ying¹⁵,Hitomi Junichi¹,Zhu Hong¹,Chen Hongbo¹,Mayo Lior⁶,Geng Jiefei¹,Amin Palak¹,DeWitt Judy Park¹,Mookhtiar Adnan Kasim¹,Florez Marcus¹,Ouchida Amanda Tomie¹,Fan Jian-bing⁷,Pasparakis Manolis⁸,Kelliher Michelle A.⁹,Ravits John³⁴,Yuan Junying¹⁵

Affiliation:

1. Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.

2. MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Cambridge, MA 02139, USA.

3. Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.

4. ALS Translational Research Program, Department of Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA.

5. Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 26 QiuYue Road, PuDong District, Shanghai, 201210, China.

6. Ann Romney Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.

7. Illumina, Inc., San Diego, CA 92122, USA.

8. Institute for Genetics, University of Cologne, 50674 Cologne, Germany.

9. Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.

Abstract

Axonal pathology and necroptosis in ALS Necroptosis, a non–caspase-dependent form of cell death, can be reduced in disease states by inhibiting a kinase called RIPK1. Until now, no human mutations have been linked to necroptosis. Ito et al. show that loss of optineurin, which is encoded by a gene that has been implicated in the human neurodegenerative disorder ALS (amyotrophic lateral sclerosis), results in sensitivity to necroptosis and axonal degeneration. When RIPK1-kinase dependent signaling is disrupted in mice that lack optineurin, necroptosis is inhibited and axonal pathology is reversed. Science , this issue p. 603

Funder

National Institute of Neurological Disorders and Stroke

National Institute on Aging

NIH

National Science and Technology Major Project of China

State Key Program of National Natural Science of China

National Institute of Allergy and Infectious Diseases

European Research Council

Daiichi Sankyo Foundation of Life Science

The Nakatomi Foundation

Mochida Memorial Foundation for Medical and Pharmaceutical Research

Japan Society for the Promotion of Science