Prion protein inhibits fast axonal transport through a mechanism involving casein kinase 2.

Autor: Zamponi E; Laboratorio de Neuropatología Experimental, Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET-Universidad Nacional de Córdoba, Córdoba, Argentina., Buratti F; Laboratorio de Neuropatología Experimental, Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET-Universidad Nacional de Córdoba, Córdoba, Argentina., Cataldi G; Laboratorio de Neuropatología Experimental, Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET-Universidad Nacional de Córdoba, Córdoba, Argentina., Caicedo HH; Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago Illinois, United States of America., Song Y; Marine Biological Laboratory, Woods Hole, Massachusetts, United States of America.; Harvard Program in Therapeutic Science, Harvard Medical School, Boston, Massachusetts, United States of America., Jungbauer LM; Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago Illinois, United States of America., LaDu MJ; Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago Illinois, United States of America., Bisbal M; Laboratorio de Neurobiología Experimental, Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET-Universidad Nacional de Córdoba, Córdoba, Argentina., Lorenzo A; Laboratorio de Neuropatología Experimental, Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET-Universidad Nacional de Córdoba, Córdoba, Argentina., Ma J; Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, Michigan, United States of America., Helguera PR; Laboratorio de Neuropatología Experimental, Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET-Universidad Nacional de Córdoba, Córdoba, Argentina., Morfini GA; Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago Illinois, United States of America.; Marine Biological Laboratory, Woods Hole, Massachusetts, United States of America., Brady ST; Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago Illinois, United States of America.; Marine Biological Laboratory, Woods Hole, Massachusetts, United States of America., Pigino GF; Laboratorio de Neuropatología Experimental, Instituto de Investigación Médica Mercedes y Martín Ferreyra, INIMEC-CONICET-Universidad Nacional de Córdoba, Córdoba, Argentina.; Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago Illinois, United States of America.; Marine Biological Laboratory, Woods Hole, Massachusetts, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2017 Dec 20; Vol. 12 (12), pp. e0188340. Date of Electronic Publication: 2017 Dec 20 (Print Publication: 2017).
DOI: 10.1371/journal.pone.0188340
Abstrakt: Prion diseases include a number of progressive neuropathies involving conformational changes in cellular prion protein (PrPc) that may be fatal sporadic, familial or infectious. Pathological evidence indicated that neurons affected in prion diseases follow a dying-back pattern of degeneration. However, specific cellular processes affected by PrPc that explain such a pattern have not yet been identified. Results from cell biological and pharmacological experiments in isolated squid axoplasm and primary cultured neurons reveal inhibition of fast axonal transport (FAT) as a novel toxic effect elicited by PrPc. Pharmacological, biochemical and cell biological experiments further indicate this toxic effect involves casein kinase 2 (CK2) activation, providing a molecular basis for the toxic effect of PrPc on FAT. CK2 was found to phosphorylate and inhibit light chain subunits of the major motor protein conventional kinesin. Collectively, these findings suggest CK2 as a novel therapeutic target to prevent the gradual loss of neuronal connectivity that characterizes prion diseases.
Databáze: MEDLINE
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