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
CNS & Neurological Disorders - Drug Targets
Title: Targeting Neurotrophic/Growth Factor Expression and Signaling for Antidepressant Drug Development
Volume: 6 Issue: 2
Author(s): Keith Q. Tanis, Samuel S. Newton and Ronald S. Duman
Affiliation:
Keywords: mitogen-activated (MAP) kinase, cyclic AMP response element binding protein (CREB), ERK Phosphorylation, Monoamine Receptor Agonists, GSK-3 Inhibitors
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.
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Cite this article as:
Tanis Q. Keith, Newton S. Samuel and Duman S. Ronald, Targeting Neurotrophic/Growth Factor Expression and Signaling for Antidepressant Drug Development, CNS & Neurological Disorders - Drug Targets 2007; 6 (2) . https://dx.doi.org/10.2174/187152707780363276
DOI https://dx.doi.org/10.2174/187152707780363276 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
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