Protein misfolding, signaling abnormalities and altered fast axonal transport: Implications for Alzheimer and Prion diseases
Autor: | Gustavo Pigino, Emiliano Zamponi |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
FAST AXONAL TRANSPORT Amyloid beta Mini Review casein kinase 2 synaptic dysfuction lcsh:RC321-571 purl.org/becyt/ford/1 [https] 03 medical and health sciences Protein Misfolding Diseases Cellular and Molecular Neuroscience 0302 clinical medicine CASEIN KINASE 2 PRION PROTEIN Prion protein protein misfolding purl.org/becyt/ford/1.6 [https] lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry biology SYNAPTIC DYSFUCTION Fast axonal transport kinesin-1 Cell biology KINESIN-1 030104 developmental biology prion protein SIGNALING PROTEIN MISFOLDING biology.protein Phosphorylation Protein folding fast axonal transport Signal transduction Casein kinase 2 signaling 030217 neurology & neurosurgery Neuroscience |
Zdroj: | CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET Frontiers in Cellular Neuroscience, Vol 13 (2019) Frontiers in Cellular Neuroscience |
Popis: | Histopathological studies revealed that progressive neuropathies including Alzheimer, and Prion diseases among others, include accumulations of misfolded proteins intracellularly, extracellularly, or both. Experimental evidence suggests that among the accumulated misfolded proteins, small soluble oligomeric conformers represent the most neurotoxic species. Concomitant phenomena shared by different protein misfolding diseases includes alterations in phosphorylation-based signaling pathways synaptic dysfunction, and axonal pathology, but mechanisms linking these pathogenic features to aggregated neuropathogenic proteins remain unknown. Relevant to this issue, results from recent work revealed inhibition of fast axonal transport (AT) as a novel toxic effect elicited by oligomeric forms of amyloid beta and cellular prion protein PrPC, signature pathological proteins associated with Alzheimer and Prion diseases, respectively. Interestingly, the toxic effect of these oligomers was fully prevented by pharmacological inhibitors of casein kinase 2 (CK2), a remarkable discovery with major implications for the development of pharmacological target-driven therapeutic intervention for Alzheimer and Prion diseases. Fil: Zamponi, Emiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina Fil: Pigino, Gustavo Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina |
Databáze: | OpenAIRE |
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