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CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Targeting Neurotrophic/Growth Factor Expression and Signaling for Antidepressant Drug Development

Author(s): Keith Q. Tanis, Samuel S. Newton and Ronald S. Duman

Volume 6 , Issue 2 , 2007

Page: [151 - 160] Pages: 10

DOI: 10.2174/187152707780363276

Price: $65

Abstract

Preclinical and clinical studies have demonstrated that stress and depression result in cell atrophy and loss in limbic and cortical brain regions while antidepressants reverse these effects. In concert with these findings, reduced expression of numerous genes that mediate neurotrophin and growth factor signaling has been observed in depressed patients and in stressed animals. Further, antidepressants are known to elevate the expression of multiple genes involved in these signaling pathways. Together, these findings have implicated neurotrophic factors in both the etiology and treatment of depression. Below we review the current data supporting the neurotrophic hypothesis of depression, and discuss potential approaches to pharmacologically upregulate neurotrophic/growth factor signaling to elicit antidepressant responses.

Keywords: mitogen-activated (MAP) kinase, cyclic AMP response element binding protein (CREB), ERK Phosphorylation, Monoamine Receptor Agonists, GSK-3 Inhibitors


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