Work

A critical role of neural-specific JNK3 for ischemic apoptosis

Year: 2003

Type: article

Abstract: c-Jun N-terminal kinase (JNK) signaling is an important contributor to stress-induced apoptosis, but it is unclear whether JNK and its isoforms (JNK1, JNK2, and JNK3) have distinct roles in cerebral ischemia. Here we show that JNK1 is the major isoform responsible for the high level of basal JNK activity in the brain. In contrast, targeted deletion of Jnk3 not only reduces the stress-induced JNK activity, but also protects mice from brain injury after cerebral ischemia-hypoxia. The downstream mechanism of JNK3-mediated apoptosis may include the induction of Bim and Fas and the mitochondrial release of cytochrome c. These results suggest that JNK3 is a potential target for neuroprotection therapies in stroke.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.2336254100

Authors: Chia-Yi Kuan, Alan J. Whitmarsh, Derek D. Yang, Guanghong Liao, Aryn J. Schloemer, Chen Dong, Jue Bao, Kenneth J. Banasiak, Gabriel G. Haddad, Richard A. Flavell, Roger J. Davis, Pasko Rakic

Institutions: Cincinnati Children's Hospital Medical Center, Howard Hughes Medical Institute, University of Massachusetts Chan Medical School, Yale University

Language: English

Topic: Cell death mechanisms and regulation

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

OpenAlex ID: W2149789552

FWCI: 9.434

Cites: 48

Cited by: 409

Related to: 10