The V81M variant of tyrosine hydroxylase is associated with more severe freezing of gait in Parkinson's disease.

ABSTRACT:

Introduction

Many of the symptoms and signs of Parkinson's disease (PD) arise from the death of midbrain dopamine neurons that utilize tyrosine hydroxylase (TH) as the rate-limiting enzyme in catecholamine biosynthesis.

Methods

We investigated whether the presence of a common TH polymorphism affects the clinical outcomes in 101 PD subjects. We further examined the effect of this polymorphism on the purified recombinant enzyme.

Results

PD subjects homozygous for the common V81M polymorphism, have higher overall freezing of gait scores after controlling for disease duration, although this polymorphism does not associate with the occurrence of PD or FOG. In vitro functional assays on pure recombinant wild type TH and V81M TH revealed that the Km of the mutant enzyme for

SUBMITTER: Tekin I 

PROVIDER: S-EPMC4770791 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature