Journal
CURRENT MEDICINAL CHEMISTRY
Volume 27, Issue 20, Pages 3314-3329Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/0929867325666181105120911
Keywords
Prolyl isomerase Pin1; Pin1 inhibitors; juglone; ATRA cancer; metabolic syndromes; fibrosis
Funding
- [17H04200]
- [16K09784]
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The prolyl isomerase Pin1 is a unique enzyme, vhich isomerizes the cis-trans conformation bet veen pSeripThr and proline and thereby regulates the function, stability and/or subcellular distribution of its target proteins. Such regulations by Pin1 are involved in numerous physiological functions as well as the pathogenic mechanisms underlying various diseases. Notably, Pin1 deficiency or inactivation is a potential cause of Alzheimer's disease, since Pin1 induces the degradation of Tau. In contrast, Pin1 overexpression is highly correlated vith the degree of malignancy of cancers, as Pin1 controls a number of oncogenes and tumor suppressors. Accordingly, Pin1 inhibitors as anti-cancer drugs have been developed. Interestingly, recent intensive studies have demonstrated Pin1 to be responsible for the onset or development of nonalcoholic steatosis, obesity, atherosclerosis, lung fibrosis, heart failure and so on, all of which have been experimentally induced in Pin1 deficient mice. In this review, we discuss the possible applications of Pin1 inhibitors to a variety of diseases including malignant tumors and also introduce the recent advances in Pin1 inhibitor research, which have been reported.
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