dc.creator | Lazić, Divna | |
dc.creator | Sagare, Abhay P | |
dc.creator | Nikolakopoulou, Angeliki M | |
dc.creator | Griffin, John H | |
dc.creator | Vassar, Robert | |
dc.creator | Zloković, Berislav V | |
dc.date.accessioned | 2019-02-22T10:10:10Z | |
dc.date.available | 2019-02-22T10:10:10Z | |
dc.date.issued | 2019 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/pubmed/30647119 | |
dc.identifier.uri | https://radar.ibiss.bg.ac.rs/handle/123456789/3263 | |
dc.description.abstract | 3K3A-activated protein C (APC), a cell-signaling analogue of endogenous blood serine protease APC, exerts vasculoprotective, neuroprotective, and anti-inflammatory activities in rodent models of stroke, brain injury, and neurodegenerative disorders. 3K3A-APC is currently in development as a neuroprotectant in patients with ischemic stroke. Here, we report that 3K3A-APC inhibits BACE1 amyloidogenic pathway in a mouse model of Alzheimer's disease (AD). We show that a 4-mo daily treatment of 3-mo-old 5XFAD mice with murine recombinant 3K3A-APC (100 µg/kg/d i.p.) prevents development of parenchymal and cerebrovascular amyloid-β (Aβ) deposits by 40-50%, which is mediated through NFκB-dependent transcriptional inhibition of BACE1, resulting in blockade of Aβ generation in neurons overexpressing human Aβ-precursor protein. Consistent with reduced Aβ deposition, 3K3A-APC normalized hippocampus-dependent behavioral deficits and cerebral blood flow responses, improved cerebrovascular integrity, and diminished neuroinflammatory responses. Our data suggest that 3K3A-APC holds potential as an effective anti-Aβ prevention therapy for early-stage AD. | en |
dc.relation | National Institutes of Health (NS090904) | |
dc.relation | National Institutes of Health (HL052246) | |
dc.rights | openAccess | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.source | The Journal of Experimental Medicine | |
dc.title | 3K3A-activated protein C blocks amyloidogenic BACE1 pathway and improves functional outcome in mice. | en |
dc.type | article | en |
dc.rights.license | BY-NC-ND | |
dcterms.abstract | Николакопоулоу, Aнгелики М; Злоковић, Берислав В; Вассар, Роберт; Гриффин, Јохн Х; Лазић, Дивна; Сагаре, Aбхаy П; | |
dc.rights.holder | © 2019 Lazic et al. | |
dc.citation.issue | 2 | |
dc.citation.volume | 216 | |
dc.identifier.doi | 10.1084/jem.20181035 | |
dc.identifier.pmid | 30647119 | |
dc.identifier.scopus | 2-s2.0-85060934988 | |
dc.identifier.wos | 000457588200005 | |
dc.citation.apa | Lazic, D., Sagare, A. P., Nikolakopoulou, A. M., Griffin, J. H., Vassar, R., & Zlokovic, B. V. (2019). 3K3A-activated protein C blocks amyloidogenic BACE1 pathway and improves functional outcome in mice. The Journal of Experimental Medicine, 216(2), 279–293. | |
dc.citation.vancouver | Lazic D, Sagare AP, Nikolakopoulou AM, Griffin JH, Vassar R, Zlokovic B V. 3K3A-activated protein C blocks amyloidogenic BACE1 pathway and improves functional outcome in mice. J Exp Med. 2019;216(2):279–93. | |
dc.citation.spage | 279 | |
dc.citation.epage | 293 | |
dc.type.version | publishedVersion | en |
dc.citation.rank | aM21 | |