ASK1 inhibition: a therapeutic strategy with multi-system benefits
| dc.contributor.author | Ogier, Jacqueline | |
| dc.contributor.author | Nayagam, Bryony | |
| dc.contributor.author | Lockhart, Paul | |
| dc.date.accessioned | 2020-02-17T03:27:11Z | |
| dc.date.available | 2020-02-17T03:27:11Z | |
| dc.date.issued | 2020-02 | |
| dc.description.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. | en_US |
| dc.description.sponsorship | The authors are supported by the Garnet Passe and Rodney Williams Memorial Foundation (PhD Research scholarship to JMO; Research Fellowship to BAN) and the Vincent Chiodo Foundation (PJL). Additional infrastructure funding to the Murdoch Children’s Research Institute was provided by the Australian Government National Health and Medical Research Council Independent Research Institute Infrastructure Support Scheme and the Victorian Government’s Operational Infrastructure Support Program. | en_US |
| dc.identifier.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]. | en_US |
| dc.identifier.issn | 0946-2716 | |
| dc.identifier.uri | http://repository.bionicsinstitute.org:8080/handle/123456789/385 | |
| dc.language.iso | en | en_US |
| dc.publisher | Springer | en_US |
| dc.subject | Apoptosis signal-regulating Kinase 1 | en_US |
| dc.subject | MAP3K5 | en_US |
| dc.subject | Clinical Trial | en_US |
| dc.subject | ROS | en_US |
| dc.subject | MAPK | en_US |
| dc.subject | p38 | en_US |
| dc.subject | JNK | en_US |
| dc.title | ASK1 inhibition: a therapeutic strategy with multi-system benefits | en_US |
| dc.type | Article | en_US |