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Title: ASK1 inhibition: a therapeutic strategy with multi-system benefits
Authors: Ogier, Jacqueline
Nayagam, Bryony
Lockhart, Paul
Keywords: Apoptosis signal-regulating Kinase 1
MAP3K5
Clinical Trial
ROS
MAPK
p38
JNK
Issue Date: Feb-2020
Publisher: Springer
Citation: Ogier, J. M., B. A. Nayagam, and P. J. Lockhart. 2020. ASK1 inhibition: a therapeutic strategy with multi-system benefits. Journal of molecular medicine: [epub ahead of print].
Abstract: p38 mitogen-activated protein kinases (P38alpha and beta) and c-Jun N-terminal kinases (JNK1, 2, and 3) are key mediators of the cellular stress response. However, prolonged P38 and JNK signalling is associated with damaging inflammatory responses, reactive oxygen species-induced cell death, and fibrosis in multiple tissues, such as the kidney, liver, central nervous system, and cardiopulmonary systems. These responses are associated with many human diseases, including arthritis, dementia, and multiple organ dysfunctions. Attempts to prevent P38- and JNK-mediated disease using small molecule inhibitors of P38 or JNK have generally been unsuccessful. However, apoptosis signal-regulating kinase 1 (ASK1), an upstream regulator of P38 and JNK, has emerged as an alternative drug target for limiting P38- and JNK-mediated disease. Within this review, we compile the evidence that ASK1 mediates damaging cellular responses via prolonged P38 or JNK activation. We discuss the potential benefits of ASK1 inhibition as a therapeutic and summarise the studies that have tested the effects of ASK1 inhibition in cell and animal disease models, in addition to human clinical trials for a variety of disorders.
URI: http://repository.bionicsinstitute.org:8080/handle/123456789/385
ISSN: 0946-2716
Appears in Collections:Other research publications

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