Coexpression of Tyrosine Hydroxylase, GTP Cyclohydrolase I, Aromatic Amino Acid Decarboxylase, and Vesicular Monoamine Transporter 2 from a Helper Virus-Free Herpes Simplex Virus Type 1 Vector Supports High-Level, Long-Term Biochemical and Behavioral Correction of a Rat Model of Parkinson's Disease
作者： Mei Sun , Lingxin Kong , Xiaodan Wang , Courtney Holmes , Qingsheng Gao
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摘要: Parkinson's disease is due to the selective loss of nigrostriatal dopaminergic neurons. Consequently, many therapeutic strategies have focused on restoring striatal dopamine levels, including direct gene transfer cells, using viral vectors that express specific biosynthetic enzymes. The central hypothesis this study coexpression four and transporter genes in neurons can support efficient production regulated, vesicular release dopamine: tyrosine hydroxylase (TH) converts L-3,4-dihydroxyphenylalanine (L-DOPA), GTP cyclohydrolase I (GTP CH I) rate-limiting enzyme biosynthesis cofactor for TH, aromatic amino acid decarboxylase (AADC) L-DOPA dopamine, a monoamine (VMAT-2) transports into synaptic vesicles, thereby supporting relieving feedback inhibition TH by dopamine. Helper virus-free herpes simplex virus...
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