title: Alterations of hHrd1 expression are related to hyperphosphorylated tau in the hippocampus in Alzheimer's disease.
abstract: The degradation of aberrantly phosphorylated tau in neurons plays an important role in the pathogenesis of Alzheimer's disease (AD). hHrd1 is a newly identified ubiquitin ligase involved in the endoplasmic reticulum (ER)-associated protein degradation. The expression and function of hHrd1 in AD brain remains elusive. In the present study, the expression of hHrd1 in AD hippocampus and the morphological relations between hHrd1 expression and pretangle formation were studied by using immunohistochemical single- and double-labeling methods. The results showed that hHrd1 was expressed in neurons and reactive astrocytes, especially in the CA2-CA4 hippocampal subfields. The ratio of hHrd1-positive neurons/astrocytes to total neurons/astrocytes was increased in the CA1 subfield in AD hippocampus compared with the age-matched controls (P < 0.05). Most Alz-50 labeled pretangles were colocalized with hHrd1, and the expression levels showed an inversed change, implied that hHrd1 might be associated with the degradation of hyperphosphorylated tau.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and Department of Neurobiology and Biophysics, School of Life Science, University of Science and Technology of China, Anhui, China.
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Hou
authors.forename: Yu-Xian
authors.initials: YX
authors.lastname: Shen
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Zhu
authors.forename: Hao
authors.initials: H
authors.lastname: Sun
authors.forename: Xue-Bo
authors.initials: XB
authors.lastname: Yan
authors.forename: Hui
authors.initials: H
authors.lastname: Fang
authors.forename: Jiang-Ning
authors.initials: JN
authors.lastname: Zhou
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000941:Antigens / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism; D002452:Cell Count; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D011180:Postmortem Changes; D018709:Statistics, Nonparametric; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C056167:Alzheimer's disease antigen; D000941:Antigens; D005904:Glial Fibrillary Acidic Protein; D016875:tau Proteins; C482345:SYVN1 protein, human; D044767:Ubiquitin-Protein Ligases