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The function of leucine-rich repeat kinase 2 in Parkinson’s disease, a study of the literature

Verkuijl, S (2014) The function of leucine-rich repeat kinase 2 in Parkinson’s disease, a study of the literature. Bachelor's Thesis, Biology.

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Parkinson’s disease is a chronic, degenerative neurological disorder characterised by the loss of dopamine producing cells in the substantia nigra. The single most common cause of familiar Parkinson’s disease are mutations in the gene encoding for leucine-rich repeat kinase 2 (LRRK2). LRRK2 is expressed throughout the body, and mutations result in symptoms that are essentially indistinguishable from those of idiopathic Parkinson’s disease. Since the identification of the LRRK2 gene in 2004 much research has focused on understanding its dysfunctional role in Parkinson’s disease. Mutations in LRRK2 gene produce an overactive protein or one with a novel function that results in cells that are less resilient to a variety of different toxins. In cell models LRRK2 overexpression has negative effects on both growth and maintenance of neurites. These cells show reductions in mitochondria content and changes in mitochondria morphology and function. Additionally, overexpression of LRRK2 results in changes in the amount of autophagosomes and affects the vesicle trafficking system. Inhibition of key players in the mitochondrial and autophagy systems has resulted in insights in the affected pathways. Mutations in LRRK2 likely disrupt autophagy function which results in mitochondrial defects and eventually Parkinson’s disease. Linking these two systems are mitochondrial fission, fusion and quality control by autophagy. Additional research into LRRK2 and the selective vulnerability of dopamine producing cells could benefit the development of preventative and treatment strategies for Parkinson’s disease.

Item Type: Thesis (Bachelor's Thesis)
Degree programme: Biology
Thesis type: Bachelor's Thesis
Language: English
Date Deposited: 15 Feb 2018 07:56
Last Modified: 15 Feb 2018 07:56

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