scholarly journals Patient-control association study of the Leucine-Rich repeat kinase 2 (LRRK2) gene in South African Parkinson's disease patients

2013 ◽  
Vol 28 (14) ◽  
pp. 2039-2040 ◽  
Author(s):  
Soraya Bardien ◽  
Janine Blanckenberg ◽  
Lize van der Merwe ◽  
Matthew J. Farrer ◽  
Owen A. Ross
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Association Study ◽  
South African ◽  
Leucine Rich Repeat ◽  
Patient Control ◽  
Lrrk2 Gene ◽  
Control Association

Cellular functions of LRRK2 implicate vesicular trafficking pathways in Parkinson's disease

2016 ◽  
Vol 44 (6) ◽  
pp. 1603-1610 ◽  
Author(s):  
Mark R. Cookson
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Intracellular Trafficking ◽  
Small Gtpases ◽  
Vesicular Trafficking ◽  
Leucine Rich Repeat ◽  
Cellular Functions ◽  
Lrrk2 Gene ◽  
Rab Family ◽  
Cellular Compartments

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene, associated with Parkinson's disease, have been shown to affect intracellular trafficking pathways in a variety of cells and organisms. An emerging theme is that LRRK2 can bind to multiple membranous structures in cells, and several recent studies have suggested that the Rab family of small GTPases might be important in controlling the recruitment of LRRK2 to specific cellular compartments. Once localized to membranes, LRRK2 then influences downstream events, evidenced by changes in the autophagy–lysosome pathway. Here, I will discuss available evidence that supports or challenges this outline, with a specific emphasis on those aspects of LRRK2 function that have been controversial or remain to be fully clarified.

scholarly journals LRRK2 in peripheral and central nervous system innate immunity: its link to Parkinson's disease

2017 ◽  
Vol 45 (1) ◽  
pp. 131-139 ◽  
Author(s):  
Heyne Lee ◽  
William S. James ◽  
Sally A. Cowley
Keyword(s):  
Parkinson’S Disease ◽  
Central Nervous System ◽  
Parkinson's Disease ◽  
Innate Immunity ◽  
Nervous System ◽  
Neurodegenerative Diseases ◽  
Cell Activation ◽  
Physiological Function ◽  
Leucine Rich Repeat ◽  
Lrrk2 Gene

Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are found in familial and idiopathic cases of Parkinson's disease (PD), but are also associated with immune-related disorders, notably Crohn's disease and leprosy. Although the physiological function of LRRK2 protein remains largely elusive, increasing evidence suggests that it plays a role in innate immunity, a process that also has been implicated in neurodegenerative diseases, including PD. Innate immunity involves macrophages and microglia, in which endogenous LRRK2 expression is precisely regulated and expression is strongly up-regulated upon cell activation. This brief report discusses the current understanding of the involvement of LRRK2 in innate immunity particularly in relation to PD, critically examining its role in myeloid cells, particularly macrophages and microglia.

scholarly journals LRRK2 Screening in a Canadian Parkinson's Disease Cohort

2007 ◽  
Vol 34 (3) ◽  
pp. 336-338 ◽  
Author(s):  
D. A. Grimes ◽  
L. Racacho ◽  
F. Han ◽  
M. Panisset ◽  
D. E. Bulman
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
High Performance Liquid Chromatography ◽  
High Performance ◽  
Sequence Variants ◽  
Leucine Rich Repeat ◽  
Novel Mutations ◽  
Intronic Sequence ◽  
G2019s Mutation ◽  
Lrrk2 Gene

Background:Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have become the most common known cause for developing Parkinson's disease. The frequency of mutations described in the literature varies widely depending on the population studied with most reports focusing only on screening for the most common G2019S mutation in exon 41.Methods:In this study seven exons (19, 24, 25, 31, 35, 38, and 41) in LRRK2 where mutations have been reported were screened in 230 unselected Parkinson's disease patients using denaturing high-performance liquid chromatography.Results:The sequencing of samples with heteroduplex profiles revealed five novel and two known intronic sequence variants. In our cohort, we were unable to detect any of the known mutations in these exons or identify novel mutations within the LRRK2 gene.Conclusions:Therefore, despite the availability of diagnostic LRRK2 genetic testing it is unlikely to yield a positive result in this population.

scholarly journals A Case-Control Association Study of RANTES (-28C>G) Polymorphism as a Risk Factor for Parkinson’s Disease in Isparta, Turkey

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Nilufer Sahin-Calapoglu ◽  
Serpil Demirci ◽  
Mustafa Calapoglu ◽  
Baris Yasar
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Association Study ◽  
Chemokine Receptors ◽  
Case Control ◽  
Pcr Rflp ◽  
Genes Encoding ◽  
Inflammatory Processes ◽  
Control Association

Background. Recent studies have revealed that inflammatory processes are involved in the pathogenesis of Parkinson’s disease (PD). Multiple lines of evidence have suggested that chemokines and their receptors are involved in several neurodegenerative disorders. We have examined whether genetic polymorphisms at the genes encoding chemokines IL-8 (-251A>T), MCP-1 (-2518A/G), and RANTES (-28C>G) and chemokine receptors CCR2 (V64I) and CCR5 (-Δ32) were associated with sporadic PD risk in Isparta, Turkey. Method. The pilot case-control association study included 30 PD patients and 60 control subjects, who were all genotyped with PCR-RFLP for the five polymorphisms. Their genotype and haplotype frequencies were compared statistically. Results. One SNP (-28C>G) in RANTES revealed a significant association with PD (P (allele) < 0.0001, p-trend = 0.0007). The risk allele (G) in the homozygous and dominant models (OR = 17.29 and 32.10, 95% CI = 0.86–347.24 and 1.74–591.937, resp.) suggests additional PD risk. The haplotype TGCAN from the IL-8 (-251A>T), MCP-1 (-2518A>G), RANTES (-28C>G), CCR-2 (V64I), and CCR-5 (-Δ32) has protective effect (OR = 0.08 [CI = 0.01–0.63], p=0.019). Conclusions. Our data are the first indication of the role of RANTES (-28C>G) in PD risk.

scholarly journals LRRK2 is not a Significant Cause of Parkinson's Disease in French-Canadians

2007 ◽  
Vol 34 (3) ◽  
pp. 333-335 ◽  
Author(s):  
Nicolas Dupré ◽  
Jean-Baptiste Rivière ◽  
Richard H. Myers ◽  
Pierre Provencher ◽  
Emmanuelle Pourcher ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Association Study ◽  
Case Control ◽  
Quebec City ◽  
Sequencing Analysis ◽  
Founder Population ◽  
French Canadian ◽  
Single Marker ◽  
Control Association

Background:An old founder mutation (G2019S) was found with high frequency in the North African Arabs (30%) and Ashkenazi Jews (18%).Objective:Demonstrate if mutations in the LRRK2 gene are a significant cause of Parkinson's disease (PD) in the French-Canadian founder population.Methods:Cases were recruited through a designated movement disorder clinic in Quebec City. Every index case had to meet the Ward and Gibb criteria for PD. Controls consisted of a non-disease group of similar age and ethnicity as the cases. Exons 31 and 41 of LRRK2 were amplified by PCR with intronic primers in all 125 PD cases and directly sequenced on an ABI 3700 sequencer. Six single nucleotide polymorphism were typed in 125 PD cases and 95 normal controls. Associations between unrelated cases and matched controls were analyzed. Single marker analysis and haplotype association tests were performed.Results:Sequencing analysis did not reveal any reported or novel mutations in exons 31 and 41 of LRRK2. The G2019S mutation as well as mutations affecting amino acid 1441 were absent in the 125 patients. The case-control association study performed to detect the presence of a common variant in LRRK2 did not provide any positive signal. Single-marker and haplotype analyses systematically gave non-significant P values.Conclusions:We performed a case-control association study in 125 French-Canadian (FC) patients with PD and 95 FC controls and found that common variants in LRRK2 are unlikely to be a significant cause of late-onset PD in this founder population.

Epigenome-Wide Association Study for Parkinson’s Disease

2014 ◽  
Vol 16 (4) ◽  
pp. 845-855 ◽  
Author(s):  
Kerry Moore ◽  
Amy Jayne McKnight ◽  
David Craig ◽  
Francis O’Neill
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Association Study
Sign in / Sign up

Export Citation Format

Share Document