With aging, AD and PD, there is growing evidence of altered structure and function of the blood-brain barrier (BBB), including modifications to tight junctions and efflux transporters, such as P-glycoprotein.
Exposure to pesticides increased the risk of alterations in different PD pathogenesis-related genes, such as GST (OR 1.97, 95% CI [1.41, 2.76]), PON-1 (OR 1.32, 95% CI [1.09, 1.6]), MDR1 (OR 2.06, 95% CI [1.58, 2.68]), and SNCA genes (OR 1.28, 95% CI [1.02, 1.37]).
This study lends support to a previous report that commonly used pesticides, specifically OCs and OPs, and variant ABCB1 genotypes at two polymorphic sites jointly increase risk of PD.
We speculated that misregulation of ABCB1 gene expression, caused by DNA sequence variants (DSVs) within its regulatory regions, may be involved in PD development.
The current meta-analysis indicates that pesticide-induced gene mutations may contribute to increasing susceptibility to PD, especially in the GSTP1, SLC6A3, and MDR1 genes.
However, the distribution of c.3435C/T differed significantly between PD patients exposed to pesticides compared to those non-exposed (odds ratio=4.74; confidence interval=[1.009; 22.306]); p=0.047), suggesting that common MDR1 variants might influence the risk to develop PD in conjunction with exposure to pesticides.
However, genotyping of 300 PD patients and 302 healthy controls did not reveal a significant association between coding MDR1 gene polymorphisms and PD.
The membrane transporter multi-drug resistance 1 (MDR1, P-gp) regulates the bioavailability of endogenous and exogenous compounds and has been implicated in disorders such as Parkinson's disease, cancer, epilepsy, human immunodeficiency virus disease, and inflammatory bowel disease.
This study investigated in vivo BBB P-gp function in patients with parkinsonian neurodegenerative syndromes, using [11C]-verapamil PET in PD, PSP and MSA patients.
Decreased blood-brain barrier (BBB) P-glycoprotein (P-gp) efflux function has been proposed as a possible causative link between toxin exposure and PD neurodegeneration.
An MDR1 haplotype containing SNPs e21/2677T and e26/3435T protects against PD in ethnic Chinese, compatible with the observation of a recent positive selection of the T alleles of these 2 SNPs in this ethnic population.
An MDR1 haplotype containing SNPs e21/2677T and e26/3435T protects against PD in ethnic Chinese, compatible with the observation of a recent positive selection of the T alleles of these 2 SNPs in this ethnic population.
Using a case control methodology, we investigated the association of MDR1 haplotypes (single nucleotide polymorphisms (SNPs) 2677 G > T/A and 3435 C > T) in a Polish PD population.