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REVIEW : Long-Term Modulation of Gene Expression in Epilepsy

Departments of Neurology, Pharmacology and Toxicology, and Biochemistry and Molecular Biophysics Virginia Commonwealth University Richmond, Virginia

T. Allen Morris

Departments of Neurology, Pharmacology and Toxicology, and Biochemistry and Molecular Biophysics Virginia Commonwealth University Richmond, Virginia

Molecular genetics has led to major advances in the study of neurological disease over the last 2 decades. Initial advances were made in understanding specific mutations that were associated with disease, such as epilepsy and other neurological conditions. In addition to specific mutations, recent research has focused on long-lasting or permanent changes in genetic expression as an underlying substrate of acquired diseases such as epilepsy. In symptomatic epilepsy, normal brain tissue is permanently altered and develops spon taneous recurrent seizures. Evidence indicates that long-lasting changes in gene expression at both tran scriptional and post-transcriptional levels are associated with epileptogenesis. The expression of transcription factors and other regulatory proteins represent a molecular mechanism for mediating these changes. Understanding the effects of severe environmental stresses on the multiple sites of transcriptional and post-transcriptional regulation of gene expression is likely to provide important insights into the devel opment of altered neuronal function in a number of important disease states, including epilepsy. NEURO SCIENTIST 5:86-99, 1999

Key Words: KEY WORDS Epilepsy • Epileptogenesis • Molecular genetics • Genetic expression • Transcnptional regulation • Post-transcriptional regulation • Transcription factors

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