Novel Pharmacological Targets for Controlling Dendrite Branching and Growth During Neuronal Development

Jose   R.   Fernandez; Bonnie   L.   Firestein

Abstract

Processing of information by the central nervous system (CNS) depends on the dendritic morphology of postsynaptic neurons. The patterning of dendrites is determined by extrinsic and intrinsic factors that promote the activation of cellular signaling pathways. These factors and signaling cascades may lead to the transcriptional activation of regulators of neuronal morphology. Interestingly, when there is an abnormal decrease in the number of dendrite branches and disruption of proper networks, neurodegenerative diseases, including Rett Syndrome, autism, and mental retardation, may result. In this review, we evaluate the potential of regulators of dendrite patterning as targets for drug design for the treatment of neurodegenerative diseases and altered neuronal growth in the CNS. Particular attention is directed towards a specific regulator of dendrite branching reported by our group, cypin (cytosolic PSD-95 interactor). We discuss this novel intrinsic regulator of dendrite branching as an innovative pharmacological target for the use of computer-aided rational drug design to control guanine levels, microtubule assembly, and neuronal differentiation during CNS development and in disease states.

Keywords: Dendrite branching, dendrite development, signaling pathways, transcriptional regulation, neurotrophins, cypin, guanine deaminase, neurological disorders