Title: Transcription Factors as Therapeutic Targets in CNS Disorders
Volume: 4
Issue: 3
Author(s): Michael J. Kane and Bruce A. Citron
Affiliation:
Keywords:
Transcription factors, Sp1, p53, PPAR, Nrf2, c-Jun, AP-1, JNK, neurodegenerative diseases, ischemia, traumatic brain injury, spinal cord injury, inflammatory response, apoptosis, neurons
Abstract: Disorders affecting the central nervous system frequently involve programmed neuronal loss. There are wellestablished changes in gene expression that occur in neurodegenerative diseases, and traumatic and ischemic injuries. Yet, we currently lack sufficient knowledge of the underlying mechanisms leading to the altered gene expression profiles affecting cell survival in the brain and spinal cord. The cell loss is accelerated by the induction of pro-cell death gene expression profiles through an altered balance of pro- and anti-apoptotic transcription factors. Dysregulation of these transcription factors constitutes one of the earliest events in these disorders and may offer a therapeutic window of opportunity for intervention across a narrow time period prior to irreversible neuronal death. There has been increasing interest in the modulation of these cell death factors to prevent or mitigate damage to neurons, with the goal of improving the lives of affected individuals. Here we review some of the recent patents that have been developed in the course of this research in the context of five different transcription factors.