Targeting neurotrophic/growth factor expression and signaling for antidepressant drug development

Keith Q. Tanis, Samuel S. Newton, Ronald S. Duman

Research output: Contribution to journalReview article

51 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)151-160
Number of pages10
JournalCNS and Neurological Disorders - Drug Targets
Volume6
Issue number2
DOIs
StatePublished - Apr 1 2007

Keywords

  • Cyclic AMP response element binding protein (CREB)
  • ERK Phosphorylation
  • GSK-3 Inhibitors
  • Mitogen-activated (MAP) kinase
  • Monoamine Receptor Agonists

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pharmacology

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