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

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

Document Type: Research Article


Affiliations: Connecticut Mental Health Center, 34 Park Street, New Haven, CT 06508, USA.

Publication date: April 1, 2007

More about this publication?
  • CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in neurological and CNS disorders. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.

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