Protein misfolding, signaling abnormalities and altered fast axonal transport: Implications for Alzheimer and Prion diseases

Autores
Zamponi, Emiliano; Pigino, Gustavo Fernando
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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
Materia
CASEIN KINASE 2
FAST AXONAL TRANSPORT
KINESIN-1
PRION PROTEIN
PROTEIN MISFOLDING
SIGNALING
SYNAPTIC DYSFUCTION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/128428
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Protein misfolding, signaling abnormalities and altered fast axonal transport: Implications for Alzheimer and Prion diseasesZamponi, EmilianoPigino, Gustavo FernandoCASEIN KINASE 2FAST AXONAL TRANSPORTKINESIN-1PRION PROTEINPROTEIN MISFOLDINGSIGNALINGSYNAPTIC DYSFUCTIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Histopathological 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; ArgentinaFil: 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; ArgentinaFrontiers Media S.A.2019-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/128428Zamponi, Emiliano; Pigino, Gustavo Fernando; Protein misfolding, signaling abnormalities and altered fast axonal transport: Implications for Alzheimer and Prion diseases; Frontiers Media S.A.; Frontiers in Cellular Neuroscience; 13; 7-2019; 1-51662-5102CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/article/10.3389/fncel.2019.00350/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fncel.2019.00350info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:08:08Zoai:ri.conicet.gov.ar:11336/128428instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 11:08:08.251CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Protein misfolding, signaling abnormalities and altered fast axonal transport: Implications for Alzheimer and Prion diseases
title Protein misfolding, signaling abnormalities and altered fast axonal transport: Implications for Alzheimer and Prion diseases
spellingShingle Protein misfolding, signaling abnormalities and altered fast axonal transport: Implications for Alzheimer and Prion diseases
Zamponi, Emiliano
CASEIN KINASE 2
FAST AXONAL TRANSPORT
KINESIN-1
PRION PROTEIN
PROTEIN MISFOLDING
SIGNALING
SYNAPTIC DYSFUCTION
title_short Protein misfolding, signaling abnormalities and altered fast axonal transport: Implications for Alzheimer and Prion diseases
title_full Protein misfolding, signaling abnormalities and altered fast axonal transport: Implications for Alzheimer and Prion diseases
title_fullStr Protein misfolding, signaling abnormalities and altered fast axonal transport: Implications for Alzheimer and Prion diseases
title_full_unstemmed Protein misfolding, signaling abnormalities and altered fast axonal transport: Implications for Alzheimer and Prion diseases
title_sort Protein misfolding, signaling abnormalities and altered fast axonal transport: Implications for Alzheimer and Prion diseases
dc.creator.none.fl_str_mv Zamponi, Emiliano
Pigino, Gustavo Fernando
author Zamponi, Emiliano
author_facet Zamponi, Emiliano
Pigino, Gustavo Fernando
author_role author
author2 Pigino, Gustavo Fernando
author2_role author
dc.subject.none.fl_str_mv CASEIN KINASE 2
FAST AXONAL TRANSPORT
KINESIN-1
PRION PROTEIN
PROTEIN MISFOLDING
SIGNALING
SYNAPTIC DYSFUCTION
topic CASEIN KINASE 2
FAST AXONAL TRANSPORT
KINESIN-1
PRION PROTEIN
PROTEIN MISFOLDING
SIGNALING
SYNAPTIC DYSFUCTION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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
description 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.
publishDate 2019
dc.date.none.fl_str_mv 2019-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/128428
Zamponi, Emiliano; Pigino, Gustavo Fernando; Protein misfolding, signaling abnormalities and altered fast axonal transport: Implications for Alzheimer and Prion diseases; Frontiers Media S.A.; Frontiers in Cellular Neuroscience; 13; 7-2019; 1-5
1662-5102
CONICET Digital
CONICET
url http://hdl.handle.net/11336/128428
identifier_str_mv Zamponi, Emiliano; Pigino, Gustavo Fernando; Protein misfolding, signaling abnormalities and altered fast axonal transport: Implications for Alzheimer and Prion diseases; Frontiers Media S.A.; Frontiers in Cellular Neuroscience; 13; 7-2019; 1-5
1662-5102
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/article/10.3389/fncel.2019.00350/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fncel.2019.00350
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media S.A.
publisher.none.fl_str_mv Frontiers Media S.A.
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1846781407541592064
score 13.179806

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