title: MicroRNA-922 promotes tau phosphorylation by downregulating ubiquitin carboxy-terminal hydrolase L1 (UCHL1) expression in the pathogenesis of Alzheimer's disease.
abstract: Decreased levels of soluble ubiquitin carboxy-terminal hydrolase L1 (UCHL1) have been reported in the brains of sporadic Alzheimer's disease (AD) patients, and the introduction of UCHL1 rescued the synaptic and cognitive function of AD model mice. Obviously, a reduction in the levels of UCHL1 may play a role in the pathogenesis of AD. However, the mechanisms underlying the regulation of UCHL1 levels in AD have not been fully elucidated. MicroRNAs (miRs) have been shown to participate in the process of AD. In our study, we discovered that microRNA-922 decreased the levels of UCHL1. Neurofibrillary tangles (NFTs) mainly consisting of the hyperphosphorylated microtubule-associated protein tau are the defining pathological features of AD. In the present study, we found the levels of UCHL1 affected the levels of phosphorylated tau: the phosphorylated tau levels increased after knockdown of UCHL1 expression, and the phosphorylated tau levels decreased when UCHL1 was overexpressed. Furthermore, overexpression of microRNA-922 increased the phosphorylated tau levels. In conclusion, miR-922 increasing the levels of phosphorylated tau by regulating UCHL1 levels contributed to the pathogenesis of AD. Our study partly explained one of the mechanisms underlying the downregulation of UCHL1 levels in AD patients and could enrich the content of tau pathology in the pathogenesis of AD.
authors.affiliation: Department of Neurology and Institute of Neurology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.
authors.forename: Z-B
authors.initials: ZB
authors.lastname: Zhao
authors.affiliation: Department of Neurology and Institute of Neurology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.
authors.forename: L
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Neurology and Institute of Neurology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.
authors.forename: R
authors.initials: R
authors.lastname: Xiong
authors.affiliation: Department of Neurology and Institute of Neurology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.
authors.forename: L-L
authors.initials: LL
authors.lastname: Wang
authors.affiliation: Department of Neurology and Institute of Neurology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.
authors.forename: B
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Neurology and Institute of Neurology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Neurology and Institute of Neurology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Neurology and Institute of Neurology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.
authors.forename: L
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Neurology and Institute of Neurology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China; Key Laboratory of Stem Cell Biology & Laboratory of Neurodegenerative Diseases, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Science and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China. Electronic address: chen_sd@medmail.com.cn.
authors.forename: S-D
authors.initials: SD
authors.lastname: Chen
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D015536:Down-Regulation; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D010766:Phosphorylation; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C577856:MIRN922 microRNA, human; D035683:MicroRNAs; C482860:UCHL1 protein, human; D016875:tau Proteins; D043222:Ubiquitin Thiolesterase
keywords: Alzheimer’s disease; UCHL1; miR-922; phosphorylated tau