title: Possible involvement of ubiquitin ligase HRD1 insolubilization in amyloid β generation.
abstract: Endoplasmic reticulum (ER)-associated degradation (ERAD) selectively retro-transports and degrades unfolded proteins accumulated in the ER. We have demonstrated that the ubiquitin ligase HRD1 involved in ERAD was significantly decreased in the cerebral cortex of Alzheimer's disease patients. Furthermore, the HRD1 level was negatively correlated with amyloid β (Aβ) production levels. Here we found that the HRD1 protein level decrease was due to its insolubilization. Moreover, these protein levels extracted from detergent insoluble fraction were positively correlated with those of SEL1L and Aβs (Aβ40 and Aβ42). Thus, the insolubilization-induced decrease in the HRD1 and SEL1L levels might involve in Aβ generation.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Chiba Institute of Science, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kaneko
authors.forename: Ryo
authors.initials: R
authors.lastname: Saito
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Okuma
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nomura
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D011506:Proteins / Q000378:metabolism*; D012995:Solubility; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D011506:Proteins; C117384:SEL1L protein, human; C482345:SYVN1 protein, human; D044767:Ubiquitin-Protein Ligases