The significance of Pin1 in the development of Alzheimer's disease.
Pin1 protein, a peptidyl-prolyl cis-trans isomerase plays an important regulatory role in neuronal function. Recent studies indicate that Pin1 may promote the dephosphorylation of tau and restore its ability to bind to and polymerize microtubles. Previous studies on postmortem human brains showed that Pin1 is down-regulated in advanced Alzheimer's disease (AD) brains compared to age-matched non-demented controls. Because AD is a slowly progressive disease with a preclinical period that can last years, the abundance and regulatory function of Pin1 may vary on the course of the disease. In order to evaluate the potential contribution of Pin1 to AD pathogenesis, levels of mRNA, protein and isomerase activity of Pin1 and phosphorylated tau from postmortem brains of 10 persons with mild-cognitive impairment (MCI), 10 with AD and 10 age-matched no cognitive impairment (NCI) were measured. The relationship between Pin1 and phosphorylated tau as well as clinical and cognitive data were analyzed. The results indicated that Pin1 activity in MCI and AD were significantly higher than in NCI. Phosphorylated tau in MCI and AD was also higher than in NCI group. The positive correlation trend in MCI and the robust correlation in AD between Pin1 activity and phosphorylated tau implies that increasing phosphorylated tau during AD pathogenesis may induce the compensatory activation/up-regulation of Pin1, while the inverse correlation between Pin1 activity and phosphorylated tau in NCI group implies that decreased Pin1 may play a role in the initial accumulation of phosphorylated tau in AD pathogenesis.
Wang
Suqing
S
Department of Pathology & Laboratory Medicine, and Waisman Center for Developmental Disabilities, University of Wisconsin School of Medicine, Madison, WI 53705, USA.
Simon
Brook P
BP
Bennett
David A
DA
Schneider
Julie A
JA
Malter
James S
JS
Wang
Deng-Shun
DS
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D003072:Cognition Disorders / Q000235:genetics / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008297:Male; D008870:Microtubules / Q000473:pathology; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D016874:Neurofibrillary Tangles / Q000473:pathology; D019696:Peptidylprolyl Isomerase / Q000235:genetics*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013223:Statistics as Topic; D016875:tau Proteins / Q000378:metabolism
C054369:MAPT protein, human; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D012333:RNA, Messenger; D016875:tau Proteins; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase