Pin1 in Alzheimer's disease.
Proteolytic processing and phosphorylation of amyloid precursor protein (APP), and hyperphosphorylation of tau protein, have been shown to be increased in Alzheimer's disease (AD) brains, leading to increased production of beta-amyloid (Abeta) peptides and neurofibrillary tangles, respectively. These observations suggest that phosphorylation events are critical to the understanding of the pathogenesis and treatment of this devastating disease. Pin-1, one of the peptidyl-prolyl isomerases (PPIase), catalyzes the isomerization of the peptide bond between pSer/Thr-Pro in proteins, thereby regulating their biological functions which include protein assembly, folding, intracellular transport, intracellular signaling, transcription, cell cycle progression and apoptosis. A number of previous studies have shown that Pin1 is co-localized with phosphorylated tau in AD brain, and shows an inverse relationship to the expression of tau. Pin1 protects neurons under in vitro conditions. Moreover, recent studies demonstrate that APP is a target for Pin1 and thus, in Abeta production. Furthermore, Pin1 was found to be oxidatively modified and to have reduced activity in the hippocampus in mild cognitive impairment (MCI) and AD. Because of the diverse functions of Pin1, and the discovery that this protein is one of the oxidized proteins common to both MCI and AD brain, the question arises as to whether Pin1 is one of the driving forces for the initiation or progression of AD pathogenesis, finally leading to neurodegeneration and neuronal apoptosis. In the present review, we discuss the role of Pin1 with respect to Alzheimer's disease.
Butterfield
D Allan
DA
Department of Chemistry, University of Kentucky, Kentucky, USA.
Abdul
Hafiz Mohmmad
HM
Opii
Wycliffe
W
Newman
Shelley F
SF
Joshi
Gururaj
G
Ansari
Mubeen Ahmad
MA
Sultana
Rukhsana
R
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism; D002453:Cell Cycle; D003072:Cognition Disorders / Q000378:metabolism / Q000523:psychology; D016207:Cytokines / Q000378:metabolism; D004249:DNA Damage; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D010084:Oxidation-Reduction; D019696:Peptidylprolyl Isomerase / Q000737:chemistry / Q000378:metabolism*; D012720:Severity of Illness Index; D013329:Structure-Activity Relationship
D016207:Cytokines; D016328:NF-kappa B; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase