Molecular biology of catecholamine-related enzymes in relation to Parkinson's disease

被引:35
作者
Nagatsu, T [1 ]
Ichinose, H [1 ]
机构
[1] Fujita Hlth Univ, Grad Sch Med, Inst Comprehens Med Sci, Toyoake, Aichi 4701192, Japan
关键词
tyrosine hydroxylase; tetrahydrobiopterin; GTP cyclohydrolase I; hereditary dystonia; juvenile parkinsonism; Parkinson's disease;
D O I
10.1023/A:1006912523846
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
1. Catecholamine (dopamine, norepinephrine, and epinephrine) biosynthesis is regulated by tyrosine hydroxylase (TH). TH activity is regulated by the concentration of the cofactor tetrahydrobiopterin (BH4), whose level is regulated by GTP cyclohydrolase I (GCH) activity. Thus, GCH activity indirectly regulates TH activity and catecholamine levels. 2. TH activity in the nigrostriatal dopaminergic neurons is most sensitive to the decrease in BH4. 3. Mutations of GCH result in reductions in GCH activity, BH4, TH activity, and dopamine, causing either recessively inherited GCH deficiency or dominantly inherited hereditary progressive dystonia [HPD; Segawa's disease; also called dopa-responsive dystonia (DRD)]. 4. In juvenile parkinsonism and Parkinson's disease, which have dopamine deficiency in the basal ganglia as HPD/DRD, the GCH gene may be normal, and the molecular mechanism of the dopamine deficiency in the basal ganglia is different from that in HPD/DRD.
引用
收藏
页码:57 / 66
页数:10
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