Wnt signaling alterations in the human spinal cord of amyotrophic lateral sclerosis cases: spotlight on Fz2 and Wnt5a

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with no cure, and elucidation of the mechanisms mediating neuronal death in this neuropathology is crucial to develop effective treatments. It has recently been demonstrated in animal models that the Wnt family of proteins is...

Descripción completa

Detalles Bibliográficos
Autores: González-Fernández, Carlos, Gonzalez, Pau, Andrés Benito, Pol, Ferrer, Isidro (Ferrer Abizanda), Rodríguez, Francisco Javier
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2019
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/141733
Acceso en línea:https://hdl.handle.net/2445/141733
Access Level:acceso abierto
Palabra clave:Éssers humans
Medul·la espinal
Esclerosi lateral amiotròfica
Human beings
Spinal cord
Amyotrophic lateral sclerosis
id ES_98a2c5abc9e5c8f1c4b981e6e0b261cc
oai_identifier_str oai:diposit.ub.edu:2445/141733
network_acronym_str ES
network_name_str España
repository_id_str
spelling Wnt signaling alterations in the human spinal cord of amyotrophic lateral sclerosis cases: spotlight on Fz2 and Wnt5aGonzález-Fernández, CarlosGonzalez, PauAndrés Benito, PolFerrer, Isidro (Ferrer Abizanda)Rodríguez, Francisco JavierÉssers humansMedul·la espinalEsclerosi lateral amiotròficaHuman beingsSpinal cordAmyotrophic lateral sclerosisAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with no cure, and elucidation of the mechanisms mediating neuronal death in this neuropathology is crucial to develop effective treatments. It has recently been demonstrated in animal models that the Wnt family of proteins is involved in this neuropathology, although its potential involvement in case of humans is almost unknown. We analyzed the expression of Wnt signaling components in healthy and ALS human spinal cords by quantitative RT-PCR, and we found that most Wnt ligands, modulators, receptors, and co-receptors were expressed in healthy controls. Moreover, we observed clear alterations in the mRNA expression of different components of this family of proteins in human spinal cord tissue from ALS cases. Specifically, we detected a significant increase in the mRNA levels of Wnt3, Wnt4, Fz2, and Fz8, together with several non-significant increases in the mRNA expression of other genes such as Wnt2b, Wnt5a, Fz3, Lrp5, and sFRP3. Based on these observations and on previous reports of studies performed in animal models, we evaluated with immunohistochemistry the protein expression patterns of Fz2 and Fz5 receptors and their main ligand Wnt5a in control samples and ALS cases. No substantial changes were observed in Fz5 protein expression pattern in ALS samples. However, we detected an increase in the amount of Fz2+ astrocytes in the borderline between gray and white matter at the ventral horn in ALS samples. Finally, Wnt5a expression was observed in neurons and astrocytes in both control and ALS samples, although Wnt5a immunolabeling in astroglial cells was significantly increased in ALS spinal cords in the same region where changes in Fz2 were observed. Altogether, these observations strongly suggest that the Wnt family of proteins, and more specifically Fz2 and Wnt5a, might be involved in human ALS pathology.Humana Press.2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/141733Articles publicats en revistes (Patologia i Terapèutica Experimental)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1007/s12035-019-1547-9Molecular Neurobiology, 2019, vol. 56, num. 10, p. 6777-6791https://doi.org/10.1007/s12035-019-1547-9(c) Humana Press., 2019info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1417332026-05-27T06:46:51Z
dc.title.none.fl_str_mv Wnt signaling alterations in the human spinal cord of amyotrophic lateral sclerosis cases: spotlight on Fz2 and Wnt5a
title Wnt signaling alterations in the human spinal cord of amyotrophic lateral sclerosis cases: spotlight on Fz2 and Wnt5a
spellingShingle Wnt signaling alterations in the human spinal cord of amyotrophic lateral sclerosis cases: spotlight on Fz2 and Wnt5a
González-Fernández, Carlos
Éssers humans
Medul·la espinal
Esclerosi lateral amiotròfica
Human beings
Spinal cord
Amyotrophic lateral sclerosis
title_short Wnt signaling alterations in the human spinal cord of amyotrophic lateral sclerosis cases: spotlight on Fz2 and Wnt5a
title_full Wnt signaling alterations in the human spinal cord of amyotrophic lateral sclerosis cases: spotlight on Fz2 and Wnt5a
title_fullStr Wnt signaling alterations in the human spinal cord of amyotrophic lateral sclerosis cases: spotlight on Fz2 and Wnt5a
title_full_unstemmed Wnt signaling alterations in the human spinal cord of amyotrophic lateral sclerosis cases: spotlight on Fz2 and Wnt5a
title_sort Wnt signaling alterations in the human spinal cord of amyotrophic lateral sclerosis cases: spotlight on Fz2 and Wnt5a
dc.creator.none.fl_str_mv González-Fernández, Carlos
Gonzalez, Pau
Andrés Benito, Pol
Ferrer, Isidro (Ferrer Abizanda)
Rodríguez, Francisco Javier
author González-Fernández, Carlos
author_facet González-Fernández, Carlos
Gonzalez, Pau
Andrés Benito, Pol
Ferrer, Isidro (Ferrer Abizanda)
Rodríguez, Francisco Javier
author_role author
author2 Gonzalez, Pau
Andrés Benito, Pol
Ferrer, Isidro (Ferrer Abizanda)
Rodríguez, Francisco Javier
author2_role author
author
author
author
dc.subject.none.fl_str_mv Éssers humans
Medul·la espinal
Esclerosi lateral amiotròfica
Human beings
Spinal cord
Amyotrophic lateral sclerosis
topic Éssers humans
Medul·la espinal
Esclerosi lateral amiotròfica
Human beings
Spinal cord
Amyotrophic lateral sclerosis
description Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with no cure, and elucidation of the mechanisms mediating neuronal death in this neuropathology is crucial to develop effective treatments. It has recently been demonstrated in animal models that the Wnt family of proteins is involved in this neuropathology, although its potential involvement in case of humans is almost unknown. We analyzed the expression of Wnt signaling components in healthy and ALS human spinal cords by quantitative RT-PCR, and we found that most Wnt ligands, modulators, receptors, and co-receptors were expressed in healthy controls. Moreover, we observed clear alterations in the mRNA expression of different components of this family of proteins in human spinal cord tissue from ALS cases. Specifically, we detected a significant increase in the mRNA levels of Wnt3, Wnt4, Fz2, and Fz8, together with several non-significant increases in the mRNA expression of other genes such as Wnt2b, Wnt5a, Fz3, Lrp5, and sFRP3. Based on these observations and on previous reports of studies performed in animal models, we evaluated with immunohistochemistry the protein expression patterns of Fz2 and Fz5 receptors and their main ligand Wnt5a in control samples and ALS cases. No substantial changes were observed in Fz5 protein expression pattern in ALS samples. However, we detected an increase in the amount of Fz2+ astrocytes in the borderline between gray and white matter at the ventral horn in ALS samples. Finally, Wnt5a expression was observed in neurons and astrocytes in both control and ALS samples, although Wnt5a immunolabeling in astroglial cells was significantly increased in ALS spinal cords in the same region where changes in Fz2 were observed. Altogether, these observations strongly suggest that the Wnt family of proteins, and more specifically Fz2 and Wnt5a, might be involved in human ALS pathology.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/141733
url https://hdl.handle.net/2445/141733
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1007/s12035-019-1547-9
Molecular Neurobiology, 2019, vol. 56, num. 10, p. 6777-6791
https://doi.org/10.1007/s12035-019-1547-9
dc.rights.none.fl_str_mv (c) Humana Press., 2019
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Humana Press., 2019
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Humana Press.
publisher.none.fl_str_mv Humana Press.
dc.source.none.fl_str_mv Articles publicats en revistes (Patologia i Terapèutica Experimental)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869414209280802816
score 15,300719

Similares en LA Referencia