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dc.contributor.authorAlikhani, Nyosha
dc.contributor.authorGuo, Lan
dc.contributor.authorYan, Shiqiang
dc.contributor.authorDu, Heng
dc.contributor.authorPinho, Catarina Moreira
dc.contributor.authorChen, John Xi
dc.contributor.authorGlaser, Elzbieta
dc.contributor.authorYan, Shirley ShiDu
dc.date.accessioned2015-05-28T14:31:34Z
dc.date.available2015-05-28T14:31:34Z
dc.date.issued2011
dc.identifier.citationAlikhani, Nyosho, Lan Guo, Shiqiang Yan, Heng Du, Catarina Moreira Pinho, John Xi Chen, Elzbieta Glaser, and Shirley ShiDu Yan. "Decreased Proteolytic Activity of the Mitochondrial Amyloid-β Degrading Enzyme, PreP Peptidasome, in Alzheimer's Disease Brain Mitochondria." Journal of Alzheimer's Disease 27.1 (2011): 75-87. Iospresss. Web. 28 May 2015. http://dx.doi.org/10.3233/JAD-2011-101716.en_US
dc.identifier.urihttp://hdl.handle.net/1808/17858
dc.descriptionThis is the published version. Copyright 2011 by Journal of Alzheimer's Disease.en_US
dc.description.abstractAccumulation of amyloid-β peptide (Aβ), the neurotoxic peptide implicated in the pathogenesis of Alzheimer's disease (AD), has been shown in brain mitochondria of AD patients and of AD transgenic mouse models. The presence of Aβ in mitochondria leads to free radical generation and neuronal stress. Recently, we identified the presequence protease, PreP, localized in the mitochondrial matrix in mammalian mitochondria as the novel mitochondrial Aβ-degrading enzyme. In the present study, we examined PreP activity in the mitochondrial matrix of the human brain's temporal lobe, an area of the brain highly susceptible to Aβ accumulation and reactive oxygen species (ROS) production. We found significantly lower hPreP activity in AD brains compared with non-AD age-matched controls. By contrast, in the cerebellum, a brain region typically spared from Aβ accumulation, there was no significant difference in hPreP activity when comparing AD samples to non-AD controls. We also found significantly reduced PreP activity in the mitochondrial matrix of AD transgenic mouse brains (Tg mAβPP and Tg mAβPP/ABAD) when compared to non-transgenic aged-matched mice. Furthermore, mitochondrial fractions isolated from AD brains and Tg mAβPP mice had higher levels of 4-hydroxynonenal, an oxidative product, as compared with those from non-AD and nonTg mice. Accordingly, activity of cytochrome c oxidase was significantly reduced in the AD mitochondria. These findings suggest that decreased PreP proteolytic activity, possibly due to enhanced ROS production, contributes to Aβ accumulation in mitochondria leading to the mitochondrial toxicity and neuronal death that is exacerbated in AD. Clearance of mitochondrial Aβ by PreP may thus be of importance in the pathology of AD.en_US
dc.publisherIOS Pressen_US
dc.titleDecreased Proteolytic Activity of the Mitochondrial Amyloid-β Degrading Enzyme, PreP Peptidasome, in Alzheimer's Disease Brain Mitochondriaen_US
dc.typeArticle
kusw.kuauthorYan, Shirley ShiDu
kusw.kudepartmentPharmacology & Toxicologyen_US
dc.identifier.doi10.3233/JAD-2011-101716
kusw.oaversionScholarly/refereed, publisher version
kusw.oapolicyThis item meets KU Open Access policy criteria.
dc.rights.accessrightsopenAccess


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