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dc.contributor.authorSong, Hen
dc.contributor.authorLi, Hen
dc.contributor.authorGuo, Sen
dc.contributor.authorPan, Yen
dc.contributor.authorFu, Yen
dc.contributor.authorZhou, Zen
dc.contributor.authorLi, Zen
dc.contributor.authorWen, Xen
dc.contributor.authorSun, Xen
dc.contributor.authorHe, Ben
dc.contributor.authorGu, Hen
dc.contributor.authorZhao, Qen
dc.contributor.authorWang, Cen
dc.contributor.authorAn, Pen
dc.contributor.authorLuo, Sen
dc.contributor.authorHu, Yen
dc.contributor.authorXie, Xen
dc.contributor.authorLu, Ben

See Huang and Gitler (doi:10.1093/brain/awy112) for a scientific commentary on this article.Lowering the levels of disease-causing proteins is an attractive treatment strategy for neurodegenerative disorders, among which Huntington's disease is an appealing disease for testing this strategy because of its monogenetic nature. Huntington's disease is mainly caused by cytotoxicity of the mutant HTT protein with an expanded polyglutamine repeat tract. Lowering the soluble mutant HTT may reduce its downstream toxicity and provide potential treatment for Huntington's disease. This is hard to achieve by small-molecule compound drugs because of a lack of effective targets. Here we demonstrate Gpr52, an orphan G protein-coupled receptor, as a potential Huntington's disease drug target. Knocking-out Gpr52 significantly reduces mutant HTT levels in the striatum and rescues Huntington's disease-associated behavioural phenotypes in a knock-in Huntington's disease mouse model expressing endogenous mutant Htt. Importantly, a novel Gpr52 antagonist E7 reduces mutant HTT levels and rescues Huntington's disease-associated phenotypes in cellular and mouse models. Our study provides an entry point for Huntington's disease drug discovery by targeting Gpr52.

dc.format.extent1782 - 1798en
dc.titleTargeting Gpr52 lowers mutant HTT levels and rescues Huntington's disease-associated phenotypes.en
dc.typeJournal Article
plymouth.organisational-group/Plymouth/00 Groups by role
plymouth.organisational-group/Plymouth/00 Groups by role/Academics
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry/Biomedical Research Group
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry/Biomedical Research Group/RC Reporting Group BRG
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry/Collaboration for the Advancement of Medical Education Research Assessment
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry/Neuroscience
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine
plymouth.organisational-group/Plymouth/Research Groups
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)
plymouth.organisational-group/Plymouth/Research Groups/Institute of Translational and Stratified Medicine (ITSMED)/CBR
dc.rights.embargoperiodNot knownen
rioxxterms.typeJournal Article/Reviewen
plymouth.funderTackling autophagy and apoptosis for the potential therapy of Huntington's Disease::MRCen

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