The small GTPase RAC1/CED-10 is essential in maintaining dopaminergic neuron function and survival against α-synuclein-induced toxicity

Parkinson's disease is associated with intracellular α-synuclein accumulation and ventral midbrain dopaminergic neuronal death in the Substantia Nigra of brain patients. The Rho GTPase pathway, mainly linking surface receptors to the organization of the actin and microtubule cytoskeletons, has...

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Autores: Kim, Hanna, Calatayud, Carles|||0000-0003-0032-4198, Guha, Sanjib, Fernandez Carasa, Irene|||0000-0002-8195-3510, Berkowitz, Laura, Carballo-Carbajal, Iria|||0000-0002-4403-8006, Ezquerra, Mario|||0000-0003-3246-6641, Fernández-Santiago, Rubén|||0000-0002-4582-0702, Kapahi, Pankaj, Raya, Ángel|||0000-0003-2189-9775, Miranda Vizuete, Antonio, Lizcano de Vega, José Miguel|||0000-0002-3154-5383, Vila Bover, Miquel|||0000-0002-1352-989X, Caldwell, Kim A., Caldwell, Guy A., Consiglio, Antonella, Dalfo, Esther|||0000-0003-4677-8515
Formato: artículo
Fecha de publicación:2018
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:219402
Acesso em linha:https://ddd.uab.cat/record/219402
https://dx.doi.org/urn:doi:10.1007/s12035-018-0881-7
Access Level:acceso abierto
Palavra-chave:Parkinson's disease
Dopaminergic neurons
Alpha-synuclein accumulation
Autophagy impairment
RAC1/ced-10
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oai_identifier_str oai:ddd.uab.cat:219402
network_acronym_str ES
network_name_str España
repository_id_str
spelling The small GTPase RAC1/CED-10 is essential in maintaining dopaminergic neuron function and survival against α-synuclein-induced toxicityKim, HannaCalatayud, Carles|||0000-0003-0032-4198Guha, SanjibFernandez Carasa, Irene|||0000-0002-8195-3510Berkowitz, LauraCarballo-Carbajal, Iria|||0000-0002-4403-8006Ezquerra, Mario|||0000-0003-3246-6641Fernández-Santiago, Rubén|||0000-0002-4582-0702Kapahi, PankajRaya, Ángel|||0000-0003-2189-9775Miranda Vizuete, AntonioLizcano de Vega, José Miguel|||0000-0002-3154-5383Vila Bover, Miquel|||0000-0002-1352-989XCaldwell, Kim A.Caldwell, Guy A.Consiglio, AntonellaDalfo, Esther|||0000-0003-4677-8515Parkinson's diseaseDopaminergic neuronsAlpha-synuclein accumulationAutophagy impairmentRAC1/ced-10Parkinson's disease is associated with intracellular α-synuclein accumulation and ventral midbrain dopaminergic neuronal death in the Substantia Nigra of brain patients. The Rho GTPase pathway, mainly linking surface receptors to the organization of the actin and microtubule cytoskeletons, has been suggested to participate to Parkinson's disease pathogenesis. Nevertheless, its exact contribution remains obscure. To unveil the participation of the Rho GTPase family to the molecular pathogenesis of Parkinson's disease, we first used C elegans to demonstrate the role of the small GTPase RAC1 (ced-10 in the worm) in maintaining dopaminergic function and survival in the presence of alpha-synuclein. In addition, ced-10 mutant worms determined an increase of alpha-synuclein inclusions in comparison to control worms as well as an increase in autophagic vesicles. We then used a human neuroblastoma cells (M17) stably over-expressing alpha-synuclein and found that RAC1 function decreased the amount of amyloidogenic alpha-synuclein. Further, by using dopaminergic neurons derived from patients of familial LRRK2-Parkinson's disease we report that human RAC1 activity is essential in the regulation of dopaminergic cell death, alpha-synuclein. 22018-01-0120182018-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/219402https://dx.doi.org/urn:doi:10.1007/s12035-018-0881-7reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengEuropean Commission https://doi.org/10.13039/501100000780 311736Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 SAF2016-77541-RMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2015-69706-RMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI15/01255Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 PI11/00072Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 BFU2016-75176-RMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 BFU2015-64408-PMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD16/0011/0024Ministerio de Educación, Cultura y Deporte https://doi.org/10.13039/501100003176 FPU12/03332Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-1460open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2194022026-06-06T12:50:31Z
dc.title.none.fl_str_mv The small GTPase RAC1/CED-10 is essential in maintaining dopaminergic neuron function and survival against α-synuclein-induced toxicity
title The small GTPase RAC1/CED-10 is essential in maintaining dopaminergic neuron function and survival against α-synuclein-induced toxicity
spellingShingle The small GTPase RAC1/CED-10 is essential in maintaining dopaminergic neuron function and survival against α-synuclein-induced toxicity
Kim, Hanna
Parkinson's disease
Dopaminergic neurons
Alpha-synuclein accumulation
Autophagy impairment
RAC1/ced-10
title_short The small GTPase RAC1/CED-10 is essential in maintaining dopaminergic neuron function and survival against α-synuclein-induced toxicity
title_full The small GTPase RAC1/CED-10 is essential in maintaining dopaminergic neuron function and survival against α-synuclein-induced toxicity
title_fullStr The small GTPase RAC1/CED-10 is essential in maintaining dopaminergic neuron function and survival against α-synuclein-induced toxicity
title_full_unstemmed The small GTPase RAC1/CED-10 is essential in maintaining dopaminergic neuron function and survival against α-synuclein-induced toxicity
title_sort The small GTPase RAC1/CED-10 is essential in maintaining dopaminergic neuron function and survival against α-synuclein-induced toxicity
dc.creator.none.fl_str_mv Kim, Hanna
Calatayud, Carles|||0000-0003-0032-4198
Guha, Sanjib
Fernandez Carasa, Irene|||0000-0002-8195-3510
Berkowitz, Laura
Carballo-Carbajal, Iria|||0000-0002-4403-8006
Ezquerra, Mario|||0000-0003-3246-6641
Fernández-Santiago, Rubén|||0000-0002-4582-0702
Kapahi, Pankaj
Raya, Ángel|||0000-0003-2189-9775
Miranda Vizuete, Antonio
Lizcano de Vega, José Miguel|||0000-0002-3154-5383
Vila Bover, Miquel|||0000-0002-1352-989X
Caldwell, Kim A.
Caldwell, Guy A.
Consiglio, Antonella
Dalfo, Esther|||0000-0003-4677-8515
author Kim, Hanna
author_facet Kim, Hanna
Calatayud, Carles|||0000-0003-0032-4198
Guha, Sanjib
Fernandez Carasa, Irene|||0000-0002-8195-3510
Berkowitz, Laura
Carballo-Carbajal, Iria|||0000-0002-4403-8006
Ezquerra, Mario|||0000-0003-3246-6641
Fernández-Santiago, Rubén|||0000-0002-4582-0702
Kapahi, Pankaj
Raya, Ángel|||0000-0003-2189-9775
Miranda Vizuete, Antonio
Lizcano de Vega, José Miguel|||0000-0002-3154-5383
Vila Bover, Miquel|||0000-0002-1352-989X
Caldwell, Kim A.
Caldwell, Guy A.
Consiglio, Antonella
Dalfo, Esther|||0000-0003-4677-8515
author_role author
author2 Calatayud, Carles|||0000-0003-0032-4198
Guha, Sanjib
Fernandez Carasa, Irene|||0000-0002-8195-3510
Berkowitz, Laura
Carballo-Carbajal, Iria|||0000-0002-4403-8006
Ezquerra, Mario|||0000-0003-3246-6641
Fernández-Santiago, Rubén|||0000-0002-4582-0702
Kapahi, Pankaj
Raya, Ángel|||0000-0003-2189-9775
Miranda Vizuete, Antonio
Lizcano de Vega, José Miguel|||0000-0002-3154-5383
Vila Bover, Miquel|||0000-0002-1352-989X
Caldwell, Kim A.
Caldwell, Guy A.
Consiglio, Antonella
Dalfo, Esther|||0000-0003-4677-8515
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Parkinson's disease
Dopaminergic neurons
Alpha-synuclein accumulation
Autophagy impairment
RAC1/ced-10
topic Parkinson's disease
Dopaminergic neurons
Alpha-synuclein accumulation
Autophagy impairment
RAC1/ced-10
description Parkinson's disease is associated with intracellular α-synuclein accumulation and ventral midbrain dopaminergic neuronal death in the Substantia Nigra of brain patients. The Rho GTPase pathway, mainly linking surface receptors to the organization of the actin and microtubule cytoskeletons, has been suggested to participate to Parkinson's disease pathogenesis. Nevertheless, its exact contribution remains obscure. To unveil the participation of the Rho GTPase family to the molecular pathogenesis of Parkinson's disease, we first used C elegans to demonstrate the role of the small GTPase RAC1 (ced-10 in the worm) in maintaining dopaminergic function and survival in the presence of alpha-synuclein. In addition, ced-10 mutant worms determined an increase of alpha-synuclein inclusions in comparison to control worms as well as an increase in autophagic vesicles. We then used a human neuroblastoma cells (M17) stably over-expressing alpha-synuclein and found that RAC1 function decreased the amount of amyloidogenic alpha-synuclein. Further, by using dopaminergic neurons derived from patients of familial LRRK2-Parkinson's disease we report that human RAC1 activity is essential in the regulation of dopaminergic cell death, alpha-synuclein.
publishDate 2018
dc.date.none.fl_str_mv 2
2018-01-01
2018
2018-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/219402
https://dx.doi.org/urn:doi:10.1007/s12035-018-0881-7
url https://ddd.uab.cat/record/219402
https://dx.doi.org/urn:doi:10.1007/s12035-018-0881-7
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission https://doi.org/10.13039/501100000780 311736
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 SAF2016-77541-R
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 SAF2015-69706-R
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI15/01255
Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 PI11/00072
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 BFU2016-75176-R
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 BFU2015-64408-P
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD16/0011/0024
Ministerio de Educación, Cultura y Deporte https://doi.org/10.13039/501100003176 FPU12/03332
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2014/SGR-1460
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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