title: Increased heat shock transcription factor 1 in the cerebellum reverses the deficiency of Purkinje cells in Alzheimer's disease.
abstract: Alzheimer's disease (AD) is one of the most debilitating neurodegenerative nerve diseases, seriously affecting one's ability to carry out daily activities. AD is both progressive and incurable, but molecular studies have begun to shed light on the mechanisms that underlie it. Immunochemical staining showed that cell bodies of Purkinje cells in the cerebellum were significantly reduced in AD rats compared with normal rats. Heat shock protein 70 (HSP70) was found to prevent polyglutamine aggregation in Huntington's disease and spinocerebellar ataxias (SCAs) and to relieve symptoms in SCAs and Parkinson's disease. Recently, AD-related phenotypes were found to be suppressed in HSP70 transgenic rats. However, the effects of other HSPs and the mechanisms of HSP-triggered changes in AD are unknown. In this study, we found that expression levels of HSP60, -70, and -90 were downregulated in the cerebella of rats with AD. Furthermore, heat shock factor 1 (HSF1), a key transcription factor for the expression of HSP genes, was found to be greatly decreased in the cerebella of AD rats. Even more interesting, injection of lentivirus vector-HSF1 into the cerebella of AD rats significantly increased HSF1 and HSP expression levels and induced an increase in the number of Purkinje cell bodies. Our findings provide novel evidence that low expression of HSPs in AD rats is dependent on the low expression of HSF1, and increased expression of HSF1 contributes to the reversal of cerebellar Purkinje cell deficiency in AD. Therefore, increasing HSF1 expression is a potential new strategy for the treatment of AD.
authors.affiliation: Third Hospital of Hebei Medical University, Shijiazhuang 050051, China.
authors.forename: Yu-Qing
authors.initials: YQ
authors.lastname: Jiang
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Wang
authors.forename: Xue-Hong
authors.initials: XH
authors.lastname: Cao
authors.forename: Zeng-You
authors.initials: ZY
authors.lastname: Ye
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Wen-Qing
authors.initials: WQ
authors.lastname: Cai
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D004195:Disease Models, Animal; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D000076249:Heat Shock Transcription Factors; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D011689:Purkinje Cells / Q000473:pathology*; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use
chemical_list: D004268:DNA-Binding Proteins; D050884:HSP72 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; C000619709:Hsf1 protein, rat; D014157:Transcription Factors