Possible Involvement of Ubiquitin Ligase HRD1 Insolubilization in Amyloid .BETA. Generation
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概要
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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.
著者
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OKUMA Yasunobu
Departmen of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University
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Kaneko Masayuki
Department Of Dental Radiology Health Sciences University Of Hokkaido
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Saito Ryo
Department Of Bioscience And Bioinformatics Faculty Of Computer Science And Systems Engineering Kyus
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Nomura Yasuyuki
Laboratory Of Pharmacotherapeutics Yokohama College Of Pharmacy
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Okuma Yasunobu
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Chiba Institute of Science
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Kaneko Masayuki
Department of Cardiology, Cardiovascular Center, Oita Oka Hospital
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Saito Ryo
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Chiba Institute of Science
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