Neuroprotective gene therapy for Parkinson's disease.

摘要: Parkinson's disease (PD) is a neurodegenerative characterised by progressive loss of the dopaminergic neurones in substantia nigra pars compacta. Accumulating evidence indicates that apoptosis contributes to neuronal cell death PD patients' brain. Excitotoxicity, oxidative stress, and mitochondrial respiratory failure are thought be key inducers apoptotic cascade. Even though initial cause mechanism degeneration poorly understood, neuroprotection can achieved interfering with either directly or preventing dysfunction. Potential agents for neurotrophic factors, inhibitors anti-oxidative agents. However, existence blood-brain barrier precludes systemic delivery these factors. In situ gene provides strategies local sustained administration protective factors at physiologically relevant doses. Viral vectors mediating stable expression central nervous system exist still under development. Efficacy has repeatedly been demonstrated animal models both ex vivo vivo. Ex could furthermore combined replacement therapies transplanting genetically modified cells compensating lost population order provide grafted degenerating host neurones. several aspects transfer, such as uncontrolled diffusion, axonal transport, unpredictable site integration immunological responses, raise safety concerns justify further development viral non-viral well genetic elements tightly controlled expression. Various available evaluation therapy strategies. These include induction specific neurone through toxins brain systemically, transgenic mice expressing human disease-associated mutations.