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2018-09-01

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cc by (c) Kim at al., 2018
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/172327

The Small GTPase RAC1/CED-10 Is Essential in Maintaining Dopaminergic Neuron Function and Survival Against alpha-Synuclein-Induced Toxicity

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Recurs relacionat

https://doi.org/10.1007/s12035-018-0881-7
 https://doi.org/10.1007/s12035-018-1010-3

Resum

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 accumulation, participates in neurite arborization and modulates autophagy. Thus, we determined for the first time that RAC1/ced-10 participates in Parkinson's disease associated pathogenesis and established RAC1/ced-10 as a new candidate for further investigation of Parkinson's disease associated mechanisms, mainly focused on dopaminergic function and survival against α-synuclein-induced toxicity.

Matèries

Malaltia de Parkinson, Malalties neurodegeneratives

Matèries (anglès)

Parkinson's disease, Neurodegenerative Diseases

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Col·leccions

Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Institut de Biomedicina (IBUB))

Citació

KIM, Hanna, CALATAYUD ARISTOY, Carles, GUHA, Sanjib, FERNANDEZ-CARASA, Irene, BERKOWITZ, Laura, CARBALLO CARBAJAL, Iria, EZQUERRA TRABALÓN, Mario, FERNANDEZ SANTIAGO, Ruben, KAPAHI, Pankaj, RAYA CHAMORRO, Ángel, MIRANDA VIZUETE, Antonio, MIGUEL LIZCANO, Jose, VILA, Miquel, CALDWELL, Kim a., CALDWELL, Guy a., CONSIGLIO, Antonella, DALFO, Esther. The Small GTPase RAC1/CED-10 Is Essential in Maintaining Dopaminergic Neuron Function and Survival Against alpha-Synuclein-Induced Toxicity. _Molecular Neurobiology_. 2018. Vol. 55, núm. 9, pàgs. 7533-7552. [consulta: 23 de gener de 2026]. ISSN: 0893-7648. [Disponible a: https://hdl.handle.net/2445/172327]

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