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http://hdl.handle.net/2445/141810
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DC Field | Value | Language |
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dc.contributor.author | Zafar, Saima | - |
dc.contributor.author | Younas, Neelam | - |
dc.contributor.author | Sheikh, Nadeem | - |
dc.contributor.author | Tahir, Waqas | - |
dc.contributor.author | Shafiq, Mohsin | - |
dc.contributor.author | Schmitz, Matthias | - |
dc.contributor.author | Ferrer, Isidro (Ferrer Abizanda) | - |
dc.contributor.author | Andréoletti, Olivier | - |
dc.contributor.author | Zerr, Inga | - |
dc.date.accessioned | 2019-10-07T15:12:27Z | - |
dc.date.available | 2019-10-08T05:10:23Z | - |
dc.date.issued | 2018-05-01 | - |
dc.identifier.issn | 0893-7648 | - |
dc.identifier.uri | http://hdl.handle.net/2445/141810 | - |
dc.description.abstract | A high priority in the prion field is to identify pre-symptomatic events and associated profile of molecular changes. Inthisstudy,wedemonstratethepre-symptomatic dysregulation of cytoskeleton assembly and its associated cofilin-1 pathway in strain and brain region-specific manners in MM1 and VV2 subtype-specific Creutzfeldt-Jakob disease at clinical and pre-clinical stage. At physiological level, PrPC interaction with cofilin-1 and phosphorylated form of cofilin (p-cofilin(Ser3)) was investigated in primary cultures of mouse cortex neurons (PCNs) of PrPC wildtype and knockout mice (PrP−/−). Short-interfering RNA downregulation of active form of cofilin-1 resulted in the redistribution/downregulation of PrPC, increase of activated form of microglia, accumulation of dense form of Factin, and upregulation of p-cofilin(Ser3). This upregulated p-cofilin(Ser3) showed redistribution of expression predominantly in the activated form of microglia in PCNs. At pathological level, cofilin-1 expression was significantly altered in cortex and cerebellum in both humans and mice at pre-clinical stage and at early symptomatic clinical stage of the disease. Further, to better understand the possible mechanism of dysregulation of cofilin-1, we also demonstrated alterations in upstream regulators; LIM kinase isoform 1 (LIMK1), slingshot phosphatase isoform 1 (SSH1), RhoA-associated kinase (Rock2), and amyloid precursor protein (APP) in sporadic Creutzfeldt-Jakob disease MM1 mice and in human MM1 and VV2 frontal cortex and cerebellum samples. In conclusion, our findings demonstrated for the first time a key pre-clinical response of cofilin-1 and the associated pathway in prion disease. | - |
dc.format.extent | 21 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Humana Press. | - |
dc.relation.isformatof | Versió postprint del document publicat a: https://doi.org/10.1007/s12035-017-0589-0 | - |
dc.relation.ispartof | Molecular Neurobiology, 2018, vol. 55, num. 5, p. 4009-4029 | - |
dc.relation.uri | https://doi.org/10.1007/s12035-017-0589-0 | - |
dc.rights | (c) Humana Press., 2018 | - |
dc.source | Articles publicats en revistes (Patologia i Terapèutica Experimental) | - |
dc.subject.classification | Malaltia de Creutzfeldt-Jakob | - |
dc.subject.classification | Patologia | - |
dc.subject.classification | Citosquelet | - |
dc.subject.classification | Metabolisme | - |
dc.subject.classification | Degeneració (Patologia) | - |
dc.subject.other | Creutzfeldt-Jakob disease | - |
dc.subject.other | Pathology | - |
dc.subject.other | Cytoskeleton | - |
dc.subject.other | Metabolism | - |
dc.subject.other | Degeneration (Pathology) | - |
dc.title | Cytoskeleton-associated risk modifiers involved in early and rapid progression of sporadic Creutzfeldt-Jakob disease | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/acceptedVersion | - |
dc.identifier.idgrec | 689482 | - |
dc.date.updated | 2019-10-07T15:12:27Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 28573459 | - |
Appears in Collections: | Articles publicats en revistes (Patologia i Terapèutica Experimental) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
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689482.pdf | 4.77 MB | Adobe PDF | View/Open |
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