Focus on the Small GTPase Rab1: A Key Player in the Pathogenesis of Parkinson’s Disease

Parkinson’s disease (PD) is the second most frequent neurodegenerative disease. It is characterized by the loss of dopaminergic neurons in the substantia nigra and the formation of large aggregates in the survival neurons called Lewy bodies, which mainly contain α-synuclein (α-syn). The cause of cel...

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Autores principales:	José Ángel Martínez-Menárguez, Emma Martínez-Alonso, Mireia Cara-Esteban, Mónica Tomás
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Rab1 GTPases Parkinson’s disease secretory pathway Golgi fragmentation autophagy Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/1d3dd12c198e47e3b56de9c25204d3f0
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spelling	oai:doaj.org-article:1d3dd12c198e47e3b56de9c25204d3f02021-11-11T17:28:36ZFocus on the Small GTPase Rab1: A Key Player in the Pathogenesis of Parkinson’s Disease10.3390/ijms2221120871422-00671661-6596https://doaj.org/article/1d3dd12c198e47e3b56de9c25204d3f02021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/12087https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Parkinson’s disease (PD) is the second most frequent neurodegenerative disease. It is characterized by the loss of dopaminergic neurons in the substantia nigra and the formation of large aggregates in the survival neurons called Lewy bodies, which mainly contain α-synuclein (α-syn). The cause of cell death is not known but could be due to mitochondrial dysfunction, protein homeostasis failure, and alterations in the secretory/endolysosomal/autophagic pathways. Survival nigral neurons overexpress the small GTPase Rab1. This protein is considered a housekeeping Rab that is necessary to support the secretory pathway, the maintenance of the Golgi complex structure, and the regulation of macroautophagy from yeast to humans. It is also involved in signaling, carcinogenesis, and infection for some pathogens. It has been shown that it is directly linked to the pathogenesis of PD and other neurodegenerative diseases. It has a protective effect against α–σψν toxicity and has recently been shown to be a substrate of LRRK2, which is the most common cause of familial PD and the risk of sporadic disease. In this review, we analyze the key aspects of Rab1 function in dopamine neurons and its implications in PD neurodegeneration/restauration. The results of the current and former research support the notion that this GTPase is a good candidate for therapeutic strategies.José Ángel Martínez-MenárguezEmma Martínez-AlonsoMireia Cara-EstebanMónica TomásMDPI AGarticleRab1GTPasesParkinson’s diseasesecretory pathwayGolgi fragmentationautophagyBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12087, p 12087 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Rab1 GTPases Parkinson’s disease secretory pathway Golgi fragmentation autophagy Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	Rab1 GTPases Parkinson’s disease secretory pathway Golgi fragmentation autophagy Biology (General) QH301-705.5 Chemistry QD1-999 José Ángel Martínez-Menárguez Emma Martínez-Alonso Mireia Cara-Esteban Mónica Tomás Focus on the Small GTPase Rab1: A Key Player in the Pathogenesis of Parkinson’s Disease
description	Parkinson’s disease (PD) is the second most frequent neurodegenerative disease. It is characterized by the loss of dopaminergic neurons in the substantia nigra and the formation of large aggregates in the survival neurons called Lewy bodies, which mainly contain α-synuclein (α-syn). The cause of cell death is not known but could be due to mitochondrial dysfunction, protein homeostasis failure, and alterations in the secretory/endolysosomal/autophagic pathways. Survival nigral neurons overexpress the small GTPase Rab1. This protein is considered a housekeeping Rab that is necessary to support the secretory pathway, the maintenance of the Golgi complex structure, and the regulation of macroautophagy from yeast to humans. It is also involved in signaling, carcinogenesis, and infection for some pathogens. It has been shown that it is directly linked to the pathogenesis of PD and other neurodegenerative diseases. It has a protective effect against α–σψν toxicity and has recently been shown to be a substrate of LRRK2, which is the most common cause of familial PD and the risk of sporadic disease. In this review, we analyze the key aspects of Rab1 function in dopamine neurons and its implications in PD neurodegeneration/restauration. The results of the current and former research support the notion that this GTPase is a good candidate for therapeutic strategies.
format	article
author	José Ángel Martínez-Menárguez Emma Martínez-Alonso Mireia Cara-Esteban Mónica Tomás
author_facet	José Ángel Martínez-Menárguez Emma Martínez-Alonso Mireia Cara-Esteban Mónica Tomás
author_sort	José Ángel Martínez-Menárguez
title	Focus on the Small GTPase Rab1: A Key Player in the Pathogenesis of Parkinson’s Disease
title_short	Focus on the Small GTPase Rab1: A Key Player in the Pathogenesis of Parkinson’s Disease
title_full	Focus on the Small GTPase Rab1: A Key Player in the Pathogenesis of Parkinson’s Disease
title_fullStr	Focus on the Small GTPase Rab1: A Key Player in the Pathogenesis of Parkinson’s Disease
title_full_unstemmed	Focus on the Small GTPase Rab1: A Key Player in the Pathogenesis of Parkinson’s Disease
title_sort	focus on the small gtpase rab1: a key player in the pathogenesis of parkinson’s disease
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/1d3dd12c198e47e3b56de9c25204d3f0
work_keys_str_mv	AT joseangelmartinezmenarguez focusonthesmallgtpaserab1akeyplayerinthepathogenesisofparkinsonsdisease AT emmamartinezalonso focusonthesmallgtpaserab1akeyplayerinthepathogenesisofparkinsonsdisease AT mireiacaraesteban focusonthesmallgtpaserab1akeyplayerinthepathogenesisofparkinsonsdisease AT monicatomas focusonthesmallgtpaserab1akeyplayerinthepathogenesisofparkinsonsdisease
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Focus on the Small GTPase Rab1: A Key Player in the Pathogenesis of Parkinson’s Disease

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