title: The nuclear inclusion a (NIa) protease of turnip mosaic virus (TuMV) cleaves amyloid-β.
abstract: BACKGROUND
  The nuclear inclusion a (NIa) protease of turnip mosaic virus (TuMV) is responsible for the processing of the viral polyprotein into functional proteins. NIa was previously shown to possess a relatively strict substrate specificity with a preference for Val-Xaa-His-Gln↓, with the scissile bond located after Gln. The presence of the same consensus sequence, Val(12)-His-His-Gln(15), near the presumptive α-secretase cleavage site of the amyloid-β (Aβ) peptide led us to hypothesize that NIa could possess activity against Aβ.
  
  
  RESULTS
  Western blotting results showed that oligomeric as well as monomeric forms of Aβ can be degraded by NIa in vitro. The specific cleavage of Aβ was further confirmed by mass spectrometry analysis. NIa was shown to exist predominantly in the cytoplasm as observed by immunofluorescence microscopy. The overexpression of NIa in B103 neuroblastoma cells resulted in a significant reduction in cell death caused by both intracellularly generated and exogenously added Aβ. Moreover, lentiviral-mediated expression of NIa in APP(sw)/PS1 transgenic mice significantly reduced the levels of Aβ and plaques in the brain.
  
  
  CONCLUSIONS
  These results indicate that the degradation of Aβ in the cytoplasm could be a novel strategy to control the levels of Aβ, plaque formation, and the associated cell death.
authors.affiliation: Department of Life Science, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
authors.forename: Hye-Eun
authors.initials: HE
authors.lastname: Han
authors.forename: Saravanan
authors.initials: S
authors.lastname: Sellamuthu
authors.forename: Bae Hyun
authors.initials: BH
authors.lastname: Shin
authors.forename: Yong Jae
authors.initials: YJ
authors.lastname: Lee
authors.forename: Sungmin
authors.initials: S
authors.lastname: Song
authors.forename: Ji-Seon
authors.initials: JS
authors.lastname: Seo
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Baek
authors.forename: Jeomil
authors.initials: J
authors.lastname: Bae
authors.forename: Hannah
authors.initials: H
authors.lastname: Kim
authors.forename: Yung Joon
authors.initials: YJ
authors.lastname: Yoo
authors.forename: Yong-Keun
authors.initials: YK
authors.lastname: Jung
authors.forename: Woo Keun
authors.initials: WK
authors.lastname: Song
authors.forename: Pyung-Lim
authors.initials: PL
authors.lastname: Han
authors.forename: Woo Jin
authors.initials: WJ
authors.lastname: Park
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D029688:Brassica napus / Q000821:virology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D003593:Cytoplasm / Q000378:metabolism; D018450:Disease Progression; D010450:Endopeptidases / Q000737:chemistry*; D015971:Gene Expression Regulation, Enzymologic; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009029:Mosaic Viruses / Q000201:enzymology* / Q000235:genetics; D009474:Neurons / Q000166:cytology; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism; D013379:Substrate Specificity; D014764:Viral Proteins / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D014764:Viral Proteins; D010450:Endopeptidases; C059992:nuclear inclusion protein a, mosaic viruses