Cytoskeleton-associated risk modifiers involved in early and rapid progression of sporadic Creutzfeldt-Jakob disease
| العنوان: | Cytoskeleton-associated risk modifiers involved in early and rapid progression of sporadic Creutzfeldt-Jakob disease |
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| المؤلفون: | Mohsin Shafiq, Isidre Ferrer, Saima Zafar, Matthias Schmitz, Olivier Andreoletti, Neelam Younas, Waqas Tahir, Nadeem Sheikh, Inga Zerr |
| المساهمون: | Universitat de Barcelona, German Center for Neurodegenerative Diseases, University of the Punjab, Institute of neuropathology, IDIBELL-University Hospital Bellvitge, University of Barcelona, Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III [Madrid] (ISC), Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées |
| المصدر: | Dipòsit Digital de la UB Universidad de Barcelona Recercat. Dipósit de la Recerca de Catalunya instname Molecular Neurobiology Molecular Neurobiology, Humana Press, 2018, 55 (5), pp.4009-4029. ⟨10.1007/s12035-017-0589-0⟩ Molecular neurobiology 55(5), 4009-4029 (2017). doi:10.1007/s12035-017-0589-0 |
| بيانات النشر: | Humana Press., 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Pathology, metabolism [Cytoskeleton], [SDV]Life Sciences [q-bio], metabolism [Microglia], MM1, Creutzfeldt-Jakob Syndrome, 0302 clinical medicine, Risk Factors, Cerebellum, Citosquelet, Amyloid precursor protein, Phosphoprotein Phosphatases, ROCK2, Phosphorylation, RNA, Small Interfering, Cells, Cultured, Degeneració (Patologia), Cytoskeleton, metabolism [Phosphoprotein Phosphatases], SSH1 protein, human, Neurons, rho-Associated Kinases, biology, Microglia, metabolism [Calcineurin], Calcineurin, Microfilament Proteins, Lim Kinases, Degeneration (Pathology), SSH1, Cofilin, Middle Aged, Patologia, Metabolisme, 3. Good health, Cell biology, metabolism [Cofilin 1], CJD, medicine.anatomical_structure, Neurology, metabolism [Lim Kinases], metabolism [Neurons], Knockout mouse, Cortex, Disease Progression, Female, Protein Binding, Cofilin 1, medicine.medical_specialty, metabolism [Actins], Cell Survival, Neuroscience (miscellaneous), metabolism [Amyloid beta-Peptides], Mice, Transgenic, macromolecular substances, LIMK1, metabolism [rho-Associated Kinases], Lim kinase, metabolism [PrPC Proteins], 03 medical and health sciences, Cellular and Molecular Neuroscience, LIMK, Downregulation and upregulation, ddc:570, medicine, Animals, Humans, Malaltia de Creutzfeldt-Jakob, PrPC Proteins, metabolism [RNA, Small Interfering], Gene Silencing, Actin, Aged, pathology [Creutzfeldt-Jakob Syndrome], Amyloid beta-Peptides, Aif1 protein, mouse, ROCK2 protein, human, Calcium-Binding Proteins, LIMK1 protein, human, metabolism [Microfilament Proteins], metabolism [Calcium-Binding Proteins], VV2, Actins, Creutzfeldt-Jakob disease, 030104 developmental biology, Metabolism, Prion protein, Rock, biology.protein, APP, 030217 neurology & neurosurgery |
| الوصف: | International audience; A high priority in the prion field is to identify pre-symptomatic events and associated profile of molecular changes. In this study, we demonstrate the pre-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 wild-type 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 F-actin, 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. |
| وصف الملف: | application/pdf |
| تدمد: | 0893-7648 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::decd9daddee4f10c42df04db2b84a74cTest http://hdl.handle.net/2445/141810Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....decd9daddee4f10c42df04db2b84a74c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 08937648 |
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