Unlabelled: Mutations in the LRRK2 gene, predominantly G2019S, have been reported in individuals with autosomal dominant inheritance and sporadic Parkinson's disease (PD). The G2019S mutation has an age-dependent penetrance and evidence shows common ancestry. The clinical manifestations are indistinguishable from idiopathic PD. Its prevalence varies according to the population studied ranging from less than 0.1% in Asians to 41% in North African Arabs. This study aimed to identify G2019S mutation in Brazilian idiopathic PD patients.
Method: We sampled 100 PD patients and 100 age- and gender-matched controls. Genetical analysis was accomplished by polymerase chain reaction (PCR).
Results: No G2019S mutations were found in both patients with sporadic PD and controls.
Conclusions: Our results may be explained by the relatively small sample size.
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http://dx.doi.org/10.1590/0004-282x20140019 | DOI Listing |
Front Neurosci
December 2024
German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Background: Extracellular vesicles are easily accessible in various biofluids and allow the assessment of disease-related changes in the proteome. This has made them a promising target for biomarker studies, especially in the field of neurodegeneration where access to diseased tissue is very limited. Genetic variants in the LRRK2 gene have been linked to both familial and sporadic forms of Parkinson's disease.
View Article and Find Full Text PDFBrain
December 2024
Lab of Parkinson's & Other Movement Disorders, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS); Parkinson's Disease and Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona; Institut de Neurociències, Universitat de Barcelona; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) CB06/05/0018-ISCIII; ES 08036 Barcelona, Spain.
Leucine-rich repeat kinase 2 (LRRK2) inhibition is a promising disease-modifying therapy for LRRK2-associated Parkinson's disease (L2PD) and idiopathic PD (iPD). However, pharmaco-dynamic readouts and progression biomarkers for clinical trials aiming for disease modification are insufficient since no endogenous marker reflecting enhanced kinase activity of the most common LRRK2 G2019S mutation has been reported yet in L2PD patients. Employing phospho-/proteomic analyses we assessed the impact that LRRK2 activating mutations had in peripheral blood mononuclear cells (PBMCs) from a LRRK2 clinical cohort from Spain (n=174).
View Article and Find Full Text PDFNPJ Parkinsons Dis
December 2024
Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada.
Oculomotor behaviour changes in patients with Parkinson's disease (PD) are a promising source of prodromal disease markers. Capitalizing on this phenomenon to facilitate early diagnosis requires oculomotor assessment in prodromal cohorts. We examined oculomotor behaviour in non-manifesting LRRK2 G2019S mutation carriers (LRRK2-NM), who have heightened PD risk.
View Article and Find Full Text PDFThe Parkinson's disease (PD)-linked protein Leucine-Rich Repeat Kinase 2 (LRRK2) consists of seven domains, including a kinase and a Roc G domain. Despite the availability of several high-resolution structures, the dynamic regulation of its unique intramolecular domain stack is nevertheless still not well understood. By in-depth biochemical analysis, assessing the Michaelis-Menten kinetics of the Roc G domain, we have confirmed that LRRK2 has, similar to other Roco protein family members, a K value of LRRK2 that lies within the range of the physiological GTP concentrations within the cell.
View Article and Find Full Text PDFInt J Mol Sci
November 2024
A.I. Virtanen Institute, University of Eastern Finland, 70211 Kuopio, Finland.
The blood-brain barrier (BBB) serves as an interface between the bloodstream and the central nervous system. It limits the movement of molecules and immune cells, regulates the entry of nutrients, and removes waste products from the brain. The dysfunction of the BBB has been identified in Parkinson's disease (PD) but the role of the BBB and endothelial cells (ECs) has not been well studied.
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