PhD Thesis (2002). Apoptosis is an etiologic component of neurodegenerative disorders [e.g. Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS)] and acute brain injury ischemia/hypoxia and trauma). Previous studies have shown that a Herpes Simplex Virus Type 2 (HSV-2) gene, ICP10 PK, activates the Ras/MEK/ERK pathway in non-neuronal cells. Because this pathway was implicated in neuronal cell survival, the present studies tested whether ICP10 PK blocks apoptosis in various experimental paradigms of neuronal apoptosis. The broad anti-apoptotic activity of ICP10 PK suggests that it may be used in gene therapy of neurological disorders that involve apoptosis. In addition, the gene can be delivered non-invasively to the central nervous system using a replication-deficient HSV-2 mutant (ICP10deltaRR).
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