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Página principal > Artículos > Artículos publicados > The small GTPase RAC1/CED-10 is essential in maintaining dopaminergic neuron function and survival against α-synuclein-induced toxicity |
Fecha: | 2018 |
Resumen: | 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. |
Ayudas: | European Commission 311736 Ministerio de Economía y Competitividad SAF2016-77541-R Ministerio de Economía y Competitividad SAF2015-69706-R Ministerio de Economía y Competitividad PI15/01255 Ministerio de Economía y Competitividad PI11/00072 Ministerio de Economía y Competitividad BFU2016-75176-R Ministerio de Economía y Competitividad BFU2015-64408-P Instituto de Salud Carlos III RD16/0011/0024 Ministerio de Educación y Ciencia FPU12/03332 Agència de Gestió d'Ajuts Universitaris i de Recerca 2014-SGR-1460 |
Derechos: | Aquest 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. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió publicada |
Materia: | Parkinson's disease ; Dopaminergic neurons ; Alpha-synuclein accumulation ; Autophagy impairment ; RAC1/ced-10 |
Publicado en: | Molecular neurobiology, Vol. 55, issue 9 (Sep. 2018) , p. 7533-7552, ISSN 1559-1182 |
20 p, 8.2 MB |