title: Focusing on the structure and the function of Pin1: new insights into the opposite effects of fever on cancers and Alzheimer's disease.
abstract: A new molecular mechanism is proposed to explain the opposite effects of fever on cancers and Alzheimer's disease (AD). The proposal is based on the experimental discovery that the fever stress interferes the structure and the activity of Pin1, which plays uniquely opposite roles in the pathogenesis of cancers and AD. Pin1 is the only known cis-trans isomerase that specifically isomerizes the pSer/pThr-Pro motifs in proteins, facilitating kinds of signaling pathways. The up-regulation of Pin1 can amplify multiple oncogenic signaling pathways, resulting in cancers, while the down-regulation of Pin1 can cause many pathological characteristics of AD. Recently, we found that Pin1 is sensitive to heat treatment, and heating can gradually damage both of the structure and the function of Pin1. So, we hypothesize that the fever stress, which is usually induced by febrile diseases or hyperthermia treatment, may lead to the damaged structure of Pin1 and the decreased activity of it in vivo, resulting in the decreased risk of cancers and the increased risk of AD. Numerous epidemiological and experimental researches on cancers and AD support the hypothesis. The hypothesis not only provides new insights into the opposite effects of fever on cancers and AD, but also gives new clues for understanding the interacting effects of the environmental and the genetic factors in the complicated pathogenesis of cancers and AD.
authors: Department of Medical Technology, Medical College, Hebei University of Engineering, Handan 056038, China. wangjingzhang1981@gmail.com
authors: Jing-Zhang
authors: JZ
authors: Wang
authors: Yu-Hua
authors: YH
authors: Zhang
authors: Xue-Wen
authors: XW
authors: Sun
authors: Ya-Li
authors: YL
authors: Li
authors: Shu-Rui
authors: SR
authors: Li
authors: Yong
authors: Y
authors: Zhang
authors: Ting
authors: T
authors: Zhang
authors: Guo-Qiang
authors: GQ
authors: Song
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000503:physiopathology*; D015536:Down-Regulation; D019317:Evidence-Based Medicine; D005334:Fever / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D008962:Models, Theoretical; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009369:Neoplasms / Q000150:complications / Q000503:physiopathology*; D019696:Peptidylprolyl Isomerase / Q000737:chemistry* / Q000502:physiology*; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase
keywords: AD; APP; Alzheimer’s disease; Aβ; NFTs; amyloid precursor protein; amyloid-β; neurofibrillary tangles