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.
Highlights
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder that is characterized by progressive memory impairment and cognitive dysfunction
The hallmarks of AD are the formation of intracellular neurofibrillary tangles composed of hyper-phosphorylated tau and extracellular amyloid plaques mainly composed of amyloid b (Ab)
We further showed that lentivirus-mediated expression of Nuclear inclusion a (NIa) in the brain of AD mice significantly reduced Ab pathology and improved behavioral deficits [23,24]
Summary
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder that is characterized by progressive memory impairment and cognitive dysfunction. Ab exists as soluble monomers and oligomers, and insoluble fibrils. Which of these forms of Ab is the active species that are responsible for synaptic loss and neurodegeneration in AD is controversial [3,4]. Neither monomeric nor fibrillar forms of Ab appear to be responsible [4,5]. A number of studies indicate that oligomeric Ab is the most potent neurotoxic species in association with AD [6,7,8,9,10]. Oligomeric Ab reduces neuronal viability approximately 10-fold more efficiently than fibrillar Ab [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
