title: GRP78 counteracts cell death and protein aggregation caused by mutant huntingtin proteins.
abstract: The ER-localized chaperone glucose-regulated protein (GRP78) protects neurons against excitotoxicity and apoptosis. Here we show that overexpressing GRP78 protects N2a cells against mutant huntingtin proteins, reduces formation of mutant huntingtin aggregates, inhibits caspase-12 activation and blocks cell death. Our data suggest that GRP78 may be a promising therapeutic target for the treatment of Huntington's disease.
authors.affiliation: Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Jiang
authors.forename: Hailong
authors.initials: H
authors.lastname: Lv
authors.forename: Min
authors.initials: M
authors.lastname: Liao
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Xu
authors.forename: Shanshan
authors.initials: S
authors.lastname: Huang
authors.forename: Huiping
authors.initials: H
authors.lastname: Tan
authors.forename: Ting
authors.initials: T
authors.lastname: Peng
authors.forename: Yinong
authors.initials: Y
authors.lastname: Zhang
authors.forename: He
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000502:physiology; D006360:Heat-Shock Proteins / Q000378:metabolism*; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D051379:Mice; D018613:Microscopy, Confocal; D050505:Mutant Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D014162:Transfection
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D050505:Mutant Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins