Please use this identifier to cite or link to this item:
Title: Cytoskeleton-associated risk modifiers involved in early and rapid progression of sporadic Creutzfeldt-Jakob disease
Author: Zafar, Saima
Younas, Neelam
Sheikh, Nadeem
Tahir, Waqas
Shafiq, Mohsin
Schmitz, Matthias
Ferrer, Isidro (Ferrer Abizanda)
Andréoletti, Olivier
Zerr, Inga
Keywords: Malaltia de Creutzfeldt-Jakob
Degeneració (Patologia)
Creutzfeldt-Jakob disease
Degeneration (Pathology)
Issue Date: 1-May-2018
Publisher: Humana Press.
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.
Note: Versió postprint del document publicat a:
It is part of: Molecular Neurobiology, 2018, vol. 55, num. 5, p. 4009-4029
Related resource:
ISSN: 0893-7648
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 SizeFormat 
689482.pdf4.77 MBAdobe PDFView/Open    Request a copy

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.