REST/NRSF Target Genes in Neuronal and Beta Cells: Pathophysiological and Therapeutic Perspectives for Diabetes and Neurodegenerative Disorders

Abstract

Pancreatic beta and neuronal cells share numerous similarities, including a key transcriptional mechanism of the differentiation programme. The mechanism involves the decrease or the extinction of the transcriptional repressor RE-1-silencing transcription factor (REST), also called neuron-restrictive silencer factor (NRSF), which leads to the expression of various genes encoding proteins required for mature beta and neuronal cell function. Abnormal expression and genetic variation in some of the REST/NRSF target genes have been reported in diabetes and neurodegenerative disorders, suggesting that common pathogenic mechanisms account for beta-cell decline and neuronal degeneration in the two diseases. In addition, some of the REST/NRSF target genes have been identified as potential therapeutic targets for improvement of beta-cell function in diabetes. This review sheds light on the neuronal and beta-cell REST/NRSF target genes that are potential future drug targets for the treatment of diabetes and neurodegeneration.