Search

Toll-like receptors (TLRs) are important mediators of inflammatory responses by recognition of many pathogen-related molecules and endogenous proteins related to immune activation. Accumulating data have recently pointed out the role of neuroinflammation in Parkinson's disease (PD) pathogenesis. In the present study, we investigated the potential role of the TLR9 -1237 T/C and TLR2 -194 to -174 del polymorphisms in PD. We studied a total of 333 individuals, 215 Greek patients with sporadic PD and 118 control subjects, using a polymerase chain reaction-restriction fragment length polymorphism method. No statistically significant differences were found between PD patients and control subjects for the TLR9 -1237 T/C genotypes or alleles. Regarding the TLR2 -196 to -174 del polymorphism, the del/del genotype and the del allele were overrepresented in the PD group compared to controls, however, this result did not reach statistical significance (P = 0.087). Further studies investigating the TLR-inflammatory background of PD are awaited to provide important insight into the aetiology of the disease.

Parkinson's disease (PD) is a complex, heterogeneous neurodegenerative disorder, affecting approximately 1% of the population over 60 years of age. The molecular and cellular mechanisms underlying PD pathogenesis are still unknown. Clathrin-mediated endocytosis (CME) is a procedure closely related to the intracellular trafficking of multiple molecules in the cell, including proteins, lipids, and neurotransmitters. Recently, variations in the gene encoding the phosphatidylinositol binding clathrin assembly protein (PICALM) has been associated with Alzheimer's disease (AD), suggesting a possible role of CME in the pathogenesis of neurodegenerative diseases. In this study, we examined for the first time the potential role of the PICALM rs3851179 polymorphism in PD. We studied the PICALM rs3851179 polymorphism in 191 Greek patients with sporadic PD and 118 control subjects, using a PCR-RFLP method. Our results do not provide evidence that the PICALM rs3851179 polymorphism increase susceptibility of PD, in the Greek population.

Mechanisms that mediate inflammatory responses may be crucial in Parkinson's disease (PD) pathogenesis. In the brain, the chemokine receptor CX3CR1 is exclusively expressed in microglia, selectively mediating microglia-neuron interaction in response to its ligand, the chemokine fractalkine. Two functional single nucleotide polymorphisms, V249I and T280M, in the coding sequence of the CX3CR1 receptor have been found to alter ligand-receptor affinity. The aim of this study was to investigate the genetic role of CX3CR1 in sporadic PD. We examined the V249I and T280M CX3CR1 polymorphisms in a case-control study of 176 sporadic PD patients and 115 controls. Polymerase chain reaction-restriction fragment length polymorphism analysis was performed for the detection of the studied CX3CR1 genotypes. This is the first study that tests CX3CR1 gene polymorphisms in patients with PD. We found no differences in genotype or haplotype frequencies between PD patients and controls, suggesting that CX3CR1 V249I and T280M polymorphisms do not increase susceptibility to PD. Additional studies should further investigate the CX3CL1-CX3CR1 axis in PD.

Brain-derived neurotrophic factor (BDNF) enhances survival of dopaminergic neurons in the substantia nigra, whereas in patients with Parkinson's disease (PD), the expression of BDNF mRNA is decreased, thus making BDNF a candidate gene for PD susceptibility. The association between BDNF Val66Met polymorphism and PD has been evaluated in several studies with controversial results. Thus, we determined the distribution of BDNF Val66Met polymorphism in 184 Greek patients with sporadic PD and 113 control participants using polymerase chain reaction-restriction fragment length polymorphism, and explored the association of the polymorphism with certain clinical parameters of the disease. Our results do not support a major role for the BDNF Val66Met polymorphism in PD in the Greek population., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

To determine whether polymorphisms in the microtubule-associated protein tau (MAPT) and/or glycogen synthase kinase-3β (GSK3β) genes underpin susceptibility to Parkinson's disease (PD), we conducted a case-control association study in a Greek cohort of 196 PD cases and 163 healthy controls. In our study, the MAPT H1 haplotype was found to be significantly associated with PD, no association was detected between the intronic rs6438552 (-157 T/C) GSK3β polymorphism and PD, whereas the C/C genotype of the promoter rs334558 (-50 T/C) GSK3β polymorphism was found to exert a protective role. The C/C genotype of the rs334558 GSK3β polymorphism was also found to have an additional protective role in our MAPT H1/H1 PD subgroup. Haplotype analysis revealed that, the T-T haplotype of both GSK3β polymorphisms was over-represented in PD patients compared to controls, and this association was independent of MAPT H1 haplotype., (Copyright © 2009 Elsevier Inc. All rights reserved.)

Mutations in beta-glucocerebrosidase gene (GBA) have been implicated in Parkinson disease (PD). A Greek cohort of 172 PD patients and 132 control individuals were screened for GBA mutations by complete sequencing of the gene's exons. Four mutations previously associated with Gaucher disease and/or Parkinson's disease (L445P, D409H, E326K, H255Q) were detected, as well as five newly identified variants (R329H, L268L, S271G, T428K, V460L), providing for the first time data regarding the frequency of GBA mutations among PD patients and controls, in the Greek population. H255Q was the most common GBA mutation among Greek PD patients (4/172). V460L was only found in control individuals (2/132). Overall, GBA mutations were significantly overrepresented in a subgroup of early onset PD patients, compared to controls (P = 0.019, OR = 4.2; 95%CI = 1.28 -- 13.82), suggesting that GBA mutations may modify age of onset for PD.