Universidad Peruana Cayetano Heredia

Uncontrolled SFK-mediated protein trafficking in prion and Alzheimer's disease

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dc.contributor.author Málaga Trillo, George Edward
dc.contributor.author Ochs, Katharina
dc.date.accessioned 2019-02-06T14:45:37Z
dc.date.available 2019-02-06T14:45:37Z
dc.date.issued 2016
dc.identifier.uri https://hdl.handle.net/20.500.12866/5113
dc.description.abstract Prions and Amyloid beta (Aβ) peptides induce synaptic damage via complex mechanisms that include the pathological alteration of intracellular signaling cascades. The host-encoded cellular prion protein (PrPC) acts as a high-affinity cell surface receptor for both toxic species and it can modulate the endocytic trafficking of the N-methyl D-aspartate (NMDA) receptor and E-cadherin adhesive complexes via Src family kinases (SFKs). Interestingly, SFK-mediated control of endocytosis is a widespread mechanism used to regulate the activity of important transmembrane proteins, including neuroreceptors for major excitatory and inhibitory neurotransmitters. Here we discuss our recent work in zebrafish and accumulating evidence suggesting that subversion of this pleiotropic regulatory mechanism by Aβ oligomers and prions explains diverse neurotransmission deficits observed in human patients and mouse models of prion and Alzheimer's neurodegeneration. While Aβ, PrPC and SFKs constitute potential therapeutic targets on their own, drug discovery efforts might benefit significantly from aiming at protein-protein interactions that modulate the endocytosis of specific SFK targets. en_US
dc.language.iso eng
dc.publisher Taylor and Francis
dc.relation.ispartofseries Prion
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Abeta peptide en_US
dc.subject Alzheimer disease en_US
dc.subject E-cadherin en_US
dc.subject endocytosis en_US
dc.subject neurotransmission en_US
dc.subject NMDA receptor en_US
dc.subject prion protein en_US
dc.subject Src family kinases en_US
dc.subject synaptic damage en_US
dc.subject zebrafish en_US
dc.subject Alzheimer Disease/enzymology/metabolism/therapy en_US
dc.subject Amyloid beta-Peptides/metabolism en_US
dc.subject Animals en_US
dc.subject Cadherins/metabolism en_US
dc.subject Endocytosis en_US
dc.subject Humans en_US
dc.subject Mice en_US
dc.subject Prion Diseases/enzymology/metabolism/therapy en_US
dc.subject Protein Transport en_US
dc.subject Signal Transduction en_US
dc.subject src-Family Kinases/metabolism en_US
dc.title Uncontrolled SFK-mediated protein trafficking in prion and Alzheimer's disease en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1080/19336896.2016.1221873
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.03
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.01
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.08
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.04
dc.relation.issn 1933-690X


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