ASK1 inhibition: a therapeutic strategy with multi-system benefits
Jacqueline M Ogier, Bryony A Nayagam, Paul J Lockhart
JOURNAL OF MOLECULAR MEDICINE-JMM | SPRINGER HEIDELBERG | Published : 2020
p38 mitogen-activated protein kinases (P38α and β) 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 (AS..View full abstract
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.