Peptidyl-prolyl isomerases: functionality and potential therapeutic targets in cardiovascular disease.
Peptidyl-prolyl cis/trans isomerases (PPIases) are a conserved group of enzymes that catalyse the conversion between cis and trans conformations of proline imidic peptide bonds. These enzymes play critical roles in regulatory mechanisms of cellular function and pathophysiology of disease. There are three different classes of PPIases and increasing interest in the development of specific PPIase inhibitors. Cyclosporine A, FK506, rapamycin and juglone are known PPIase inhibitors. Herein, we review recent advances in elucidating the role and regulation of the PPIase family in vascular disease. We focus on peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1), an important member of the PPIase family that plays a role in cell cycle progression, gene expression, cell signalling and cell proliferation. In addition, Pin1 may be involved in atherosclerosis. The unique role of Pin1 as a molecular switch that impacts on multiple downstream pathways necessitates the evaluation of a highly specific Pin1 inhibitor to aid in potential therapeutic drug discovery.
Discipline of Pharmacy, RMIT University, Melbourne, Vic., Australia; Diabetes Complications Group, Metabolism, Exercise and Disease Program, Health Innovations Research Institute, RMIT University, Melbourne, Vic., Australia; International Islamic University Malaysia, Kuala Lumpur, Malaysia.
Muhamad A
MA
Rostam
Terrence J
TJ
Piva
Hossein B
HB
Rezaei
Danielle
D
Kamato
Peter J
PJ
Little
Wenhua
W
Zheng
Narin
N
Osman
D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism*; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology
D000072340:NIMA-Interacting Peptidylprolyl Isomerase; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase
Pin1; atherosclerosis; cardiovascular disease; peptidyl-prolyl isomerase