Ancient Origin of the Parkinson Disease Gene LRRK2

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LRRK2 and Parkinson disease.

OBJECTIVES To review the molecular genetics and functional biology of leucine-rich repeat kinase 2 (LRRK2) in parkinsonism and to summarize the opportunities and challenges to develop interventions for Parkinson disease (PD) based on this genetic insight. DATA SOURCES Publications cited are focused on LRRK2 biology between 2004 and March 2009. STUDY SELECTION Literature selected was based o...

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The Parkinson disease gene LRRK2: evolutionary and structural insights.

Mutations in the human leucine-rich repeat kinase 2 (LRRK2) gene are associated with both familial and sporadic Parkinson disease (PD). LRRK2 belongs to a gene family known as Roco. Roco genes encode for large proteins with several protein domains. Particularly, all Roco proteins have a characteristic GTPase domain, named Roc, plus a domain of unknown function called COR. In addition, LRRK2 and...

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Contribution of GTPase activity to LRRK2-associated Parkinson disease

Mutations in the leucine-rich repeat kinase 2 (LRRK2, PARK8, OMIM 607060) gene represent the most common known cause of hereditary Parkinson's disease (PD) with late-onset and dominant inheritance. LRRK2 protein is composed of multiple domains including two distinct enzymatic domains, a kinase and a Ras-of-complex (Roc) GTPase, connected by a C-terminal-of-Roc (COR) domain, and belongs to the R...

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Achieving neuroprotection with LRRK2 kinase inhibitors in Parkinson disease

In the translation of discoveries from the laboratory to the clinic, the track record in developing disease-modifying therapies in neurodegenerative disease is poor. A carefully designed development pipeline built from discoveries in both pre-clinical models and patient populations is necessary to optimize the chances for success. Genetic variation in the leucine-rich repeat kinase two gene (LR...

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Parkinson disease, cancer, and LRRK2: causation or association?

Neurology 2012;78:772–773 At a superficial level, Parkinson disease (PD) and cancer seem to be like the 2 sides of a coin: uncontrolled cell growth in cancer contrasting with untimely cell death in PD. The underlying mechanisms could therefore be 2 opposite endpoints of those intracellular pathways that regulate the cell cycle, cell death, and cell survival.1 Extrapolating this point, if there ...

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ژورنال

عنوان ژورنال: Journal of Molecular Evolution

سال: 2008

ISSN: 0022-2844,1432-1432

DOI: 10.1007/s00239-008-9122-4