title: Intracellular cleavage of amyloid β by a viral protease NIa prevents amyloid β-mediated cytotoxicity.
abstract: Nuclear inclusion a (NIa) of turnip mosaic virus is a cytosolic protease that cleaves amyloid β (Aβ) when heterologously overexpressed. Lentivirus-mediated expression of NIa in the brains of APP(sw)/PS1 mice significantly reduces cerebral Aβ levels and plaque depositions, and improves behavioral deficits. Here, the effects of NIa and neprilysin (NEP), a well-known Aβ-cleaving protease, on oligomeric Aβ-induced cell death were evaluated. NIa cleaved monomeric and oligomeric Aβ at a similar rate, whereas NEP only cleaved monomeric Aβ. Oligomeric Aβ-induced cytotoxicity and mitochondrial dysfunction were significantly ameliorated by NIa, but not by NEP. Endocytosed fluorescently-labeled Aβ localized to mitochondria, and this was significantly reduced by NIa, but not by NEP. These data suggest that NIa may exerts its protective roles by degrading Aβ and thus preventing mitochondrial deposition of Aβ.
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea; Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Baehyun
authors.initials: B
authors.lastname: Shin
authors.affiliation: Bio Imaging and Cell Dynamics Research Center, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea; Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Oh
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.
authors.forename: Sang Min
authors.initials: SM
authors.lastname: Park
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.
authors.forename: Hye-Eun
authors.initials: HE
authors.lastname: Han
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.
authors.forename: Michael
authors.initials: M
authors.lastname: Ye
authors.affiliation: Bio Imaging and Cell Dynamics Research Center, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.
authors.forename: Woo Keun
authors.initials: WK
authors.lastname: Song
authors.affiliation: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.
authors.forename: Woo Jin
authors.initials: WJ
authors.lastname: Park
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D002460:Cell Line; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D055503:Protein Multimerization; D059748:Proteolysis; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D014764:Viral Proteins; D012321:DNA-Directed RNA Polymerases; D010450:Endopeptidases