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Abstract <p>Gene therapy is considered a promising approach for the treatmentof Parkinson’s disease (PD). Tyrosine hydroxylase (TH) is the primaryrate-limiting enzyme for dopamine synthesis in dopaminergic neurons,while dopamine decarboxylase (DDC) and GTP cyclohydrolase 1 (GCH1)are essential and regulatory enzymes that are crucial for supporting efficientdopamine production and secretion. In this study, a recombinantlentivirus overexpressing TH, DDC, and GCH1 genes was constructedand transplanted into the right medial forebrain bundle (MFB) of6-hydroxydopamine (6-OHDA) induced PD rat models. Behavioral analysesat 4 and 8 weeks post-transplantation demonstrated significant functionalrecovery in PD rats overexpressing the genes, alleviating Parkinsonianbehavioral deficits. Histological studies revealed a notable increasein TH-positive cells in the brains of PD rats overexpressing thegenes, with the overexpressed genes being expressed in various cellsand promoting dopamine secretion. Western blot and enzyme-linkedimmunosorbent assay analyses also showed a significant elevationin TH expression in the midbrain proteins and dopamine secretionin the cerebrospinal fluid of PD rats, surpassing half of the levelsobserved in normal rats. This study confirms the potential of lentivirus-mediatedgene transplantation for PD therapy, highlighting the role of overexpressedTH, DDC, and GCH1 genes in the treatment of PD rats.</p>

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Therapeutic Effects of Recombinant Lentivirus Overexpressing TH, DDC, and GCH1 Genes in the 6-hydroxydopamine Induced Parkinson’s Disease Rat

  • 期刊论文

  • 发表日期：

    2026年2月26日

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  • Junyan Chang,
  • Xiaolong Huang,
  • Yiqin He,
  • Yang Liu,
  • Xiangshu Meng,
  • Caiyun Ma,
  • Gaofeng Liu,
  • Changqing Liu,
  • Yu Guo,
  • Chunjing Wang

摘要

Abstract

Gene therapy is considered a promising approach for the treatmentof Parkinson’s disease (PD). Tyrosine hydroxylase (TH) is the primaryrate-limiting enzyme for dopamine synthesis in dopaminergic neurons,while dopamine decarboxylase (DDC) and GTP cyclohydrolase 1 (GCH1)are essential and regulatory enzymes that are crucial for supporting efficientdopamine production and secretion. In this study, a recombinantlentivirus overexpressing TH, DDC, and GCH1 genes was constructedand transplanted into the right medial forebrain bundle (MFB) of6-hydroxydopamine (6-OHDA) induced PD rat models. Behavioral analysesat 4 and 8 weeks post-transplantation demonstrated significant functionalrecovery in PD rats overexpressing the genes, alleviating Parkinsonianbehavioral deficits. Histological studies revealed a notable increasein TH-positive cells in the brains of PD rats overexpressing thegenes, with the overexpressed genes being expressed in various cellsand promoting dopamine secretion. Western blot and enzyme-linkedimmunosorbent assay analyses also showed a significant elevationin TH expression in the midbrain proteins and dopamine secretionin the cerebrospinal fluid of PD rats, surpassing half of the levelsobserved in normal rats. This study confirms the potential of lentivirus-mediatedgene transplantation for PD therapy, highlighting the role of overexpressedTH, DDC, and GCH1 genes in the treatment of PD rats.