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Title: | Targeting apoptosis signal-regulating kinase 1 in acute and chronic kidney disease. | Authors: | Nikolic-Paterson D.J. ;Tesch G.H.;Ma F.Y. | Institution: | (Tesch, Ma, Nikolic-Paterson) Department of Nephrology, Monash University, VIC, Australia (Tesch, Ma, Nikolic-Paterson) Department of Medicine, Monash Medical Centre, Clayton, VIC, Australia | Issue Date: | 27-Oct-2020 | Copyright year: | 2020 | Publisher: | Blackwell Publishing Inc. (E-mail: subscrip@blackwellpub.com) | Place of publication: | United States | Publication information: | Anatomical Record. 303 (10) (pp 2553-2560), 2020. Date of Publication: 01 Oct 2020. | Journal: | Anatomical Record | Abstract: | Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein kinase (MAP3K) family which acts as an upstream regulator for the activation of p38 MAPK and c-Jun N-terminal kinase (JNK). Experimental studies have demonstrated a pathogenic role for p38 MAPK and JNK activation in a number of kidney disease models; however, clinical studies targeting these kinases directly have been problematic due to their role in homeostatic functions. In comparison, ASK1 is activated in pathological states and is not essential for homeostatic functions, suggesting that ASK1 may be a safe and effective therapeutic target to inhibit p38 MAPK and JNK signaling in disease. Animal model studies using Ask1 gene deficient mice or a selective ASK1 inhibitor have demonstrated that ASK1 blockade is effective in a variety of acute and chronic kidney diseases; preventing cell injury, inflammation, fibrosis, albuminuria, and renal function impairment. Positive outcomes from these experimental studies have led to the current evaluation of an ASK1 inhibitor in patients with moderate to advanced diabetic kidney disease. This review summarizes the preclinical studies of ASK1 blockade in models of acute and chronic kidney injury and a clinical study examining ASK1 inhibitor treatment in diabetic kidney disease.Copyright © 2020 American Association for Anatomy | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1002/ar.24373 | PubMed URL: | 31971352 [http://www.ncbi.nlm.nih.gov/pubmed/?term=31971352] | ISSN: | 1932-8486 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/29128 | Type: | Article | Subjects: | *chronic kidney failure diabetic nephropathy/dt [Drug Therapy] enzyme activation enzyme inhibition human priority journal protein targeting *apoptosis signal regulating kinase 1/ec [Endogenous Compound] protein serine threonine kinase inhibitor/dt [Drug Therapy] protein serine threonine kinase inhibitor/pv [Special Situation for Pharmacovigilance] nonhuman *acute kidney failure article cardiorenal syndrome protein targeting human enzyme inhibition enzyme activation diabetic nephropathy / drug therapy nonhuman *chronic kidney failure priority journal cardiorenal syndrome Article *acute kidney failure |
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