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Role of tau kinases (CDK5R1 and GSK3B) in Parkinson's disease: a study from India.

Abstract：

:Glycogen synthase kinase-3β (GSK3B) and cyclin-dependent kinase 5 (CDK5) are the 2 major protein kinases involved in abnormal phosphorylation of tau. To determine their potential role in the pathogenesis of Parkinson's disease (PD) we analyzed 2 functional single nucleotide polymorphisms (SNPs) of GSK3B (rs334558 and rs6438552) and rs735555 of CDK5 regulatory subunit 1 (CDK5R1) in 373 PD cases and 346 healthy controls of eastern India. The C,C and T,C haplotypes of GSK3B were respectively moderately associated with increased risk and protection for late onset PD (LOPD) (odds ratio [OR], 1.399; 95% confidence interval [CI], 1.069-1.829; p = 0.015, and OR, 0.436; 95% CI, 0.222-0.853; p = 0.016, respectively). Moreover, moderate to significant interaction between different loci were observed for the entire PD cohort or late onset PD only. However, among these interactions, individuals carrying the (C/C) genotype at both loci (rs6438552 and rs735555) had almost twice the risk of developing PD than those without this genotypic combination (OR, 1.871; 95% CI, 1.181-2.964; p = 0.009). Thus, synergistic effect between the 2 major tau kinases, through these SNPs, appears to determine the risk profile for PD.

journal_name

Neurobiol Aging

journal_title

Neurobiology of aging

authors

Das G,Misra AK,Das SK,Ray K,Ray J

doi

10.1016/j.neurobiolaging.2010.10.016

subject

Has Abstract

pub_date

2012-07-01 00:00:00

pages

1485.e9-15

issue

7

eissn

0197-4580

issn

1558-1497

pii

S0197-4580(10)00461-6

journal_volume

33

pub_type

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