Brain GTP cyclohydrolase I protein reduction in dopa-responsive dystonia: a clue to the pathogenesis.

许多多巴反应性肌张力障碍(DRD)患者显示出编码GTP环水解酶I(GTPCH)的基因突变。然而，目前还没有关于受试者脑内GTPCH蛋白水平的报道，DRD患者纹状体GTPCH的实际状态尚不清楚。我们首次在尸检的人脑组织中检测到GTPCH蛋白浓度，发现：1)该蛋白在纹状体中的表达水平很高，2)GTPCH蛋白在GTPCH缺陷DRD患者壳核中的浓度显著降低(-76%[均值])，在帕金森病患者中显著降低(-53%)，3)GTPCH蛋白在出生后早期(1-28天)升高，儿童期达到平台期，成年后(17-99岁)下降。

Many patients with dopa-responsive dystonia (DRD) have shown mutations in the gene encoding GTP cyclohydrolase I (GTPCH). However, there have been no reports of GTPCH protein levels in the brain of human subjects and the actual status of striatal GTPCH in DRD is unknown. We measured GTPCH protein concentrations for the first time in the autopsied human brain and found the following; 1) the expression level of this protein was high in the striatum, 2) concentrations of GTPCH protein in the putamen were substantially decreased in patients with GTPCH-deficient DRD (-76% [mean]) and were significantly reduced in patients with Parkinson disease (-53%), and 3) GTPCH protein levels in the putamen increased in early postnatal period (1-28 days), reached a plateau in childhood, and decreased in adulthood (17-99 years).