Knock-Out and Transgenic Strategies to Improve Neural Transplantation Therapy for Parkinson's Disease

摘要

The remaining obstacles to achieving reliable therapeutic effects by neurotransplantation for Parkinson's disease (PD) are: (1) poor survival of grafted fetal neurons, and (2) insufficient axonal outgrowth and functional recovery. Our experiments were aimed at preventing cell death by pre-treatment of fetal cells with pharmacological inhibitors of caspases and complement inhibitors. To enhance axonal growth leading to optimal functional recovery by neuronal transplants, we employed transgenic bcl-2 overexpressing donor cells and similar molecules influencing the growth of axons in the fetal and adult CNS. Such molecules significantly improved neural transplantation outcomes and regeneration. Our results indicate that hubcl-2 expression can enhance dopaminergic axonal outgrowth in vivo. Immunophilin ligands and GDNF can also generate increased axonal elongation and branching of dopamine neurons in neural transplants.