A review. Regulation of gene expression represents a major component in antidepressant drug action. The effect of antidepressant treatments on the function of cAMP-responsive element binding protein (CREB), a transcription factor that regulates expression of several genes involved in neuroplasticity, cell survival, and cognition, has been extensively studied. Although there is general agreement that chronic antidepressants stimulate CREB function, conflicting results suggest that different effects may depend on drug type, drug dosage, and different exptl. paradigms. CREB function is activated by a vast array of physiol. stimuli, conveyed through a no. of signaling pathways acting in concert, but thus far the effects of antidepressants on CREB have been analyzed mostly with regard to the cAMP-protein kinase A pathway. A growing body of data shows that other major pathways, such as the calcium/calmodulin-dependent kinase and the mitogen-activated kinase cascades, are involved in activity-dependent regulation of gene expression and may also be implicated in the mechanism of action of antidepressants. In this article the available evidence is reviewed with an attempt to identify the reasons for exptl. discrepancies and possible directions for future research. Particular emphasis is given to the regulation of brain-derived neurotrophic factor (BDNF), a CREB-regulated gene, which has been implicated in both the pathophysiol. and pharmacol. of mood disorders. The array of different results obtained by various groups is analyzed with an eye on recent advancements in the regulation of BDNF transcription, in an attempt to understand better the mechanisms of drug action and dissect mol. requirements for faster and more efficient antidepressant treatment

Tardito, D., Perez, J., Tiraboschi, E., Musazzi, L., Racagni, G., Popoli, M. (2006). Signaling pathways regulating gene expression, neuroplasticity, and neurotrophic mechanisms in the action of antidepressants : a critical overview. PHARMACOLOGICAL REVIEWS, 58(1), 115-134 [10.1124/pr.58.1.7].

Signaling pathways regulating gene expression, neuroplasticity, and neurotrophic mechanisms in the action of antidepressants : a critical overview

L. Musazzi;
2006

Abstract

A review. Regulation of gene expression represents a major component in antidepressant drug action. The effect of antidepressant treatments on the function of cAMP-responsive element binding protein (CREB), a transcription factor that regulates expression of several genes involved in neuroplasticity, cell survival, and cognition, has been extensively studied. Although there is general agreement that chronic antidepressants stimulate CREB function, conflicting results suggest that different effects may depend on drug type, drug dosage, and different exptl. paradigms. CREB function is activated by a vast array of physiol. stimuli, conveyed through a no. of signaling pathways acting in concert, but thus far the effects of antidepressants on CREB have been analyzed mostly with regard to the cAMP-protein kinase A pathway. A growing body of data shows that other major pathways, such as the calcium/calmodulin-dependent kinase and the mitogen-activated kinase cascades, are involved in activity-dependent regulation of gene expression and may also be implicated in the mechanism of action of antidepressants. In this article the available evidence is reviewed with an attempt to identify the reasons for exptl. discrepancies and possible directions for future research. Particular emphasis is given to the regulation of brain-derived neurotrophic factor (BDNF), a CREB-regulated gene, which has been implicated in both the pathophysiol. and pharmacol. of mood disorders. The array of different results obtained by various groups is analyzed with an eye on recent advancements in the regulation of BDNF transcription, in an attempt to understand better the mechanisms of drug action and dissect mol. requirements for faster and more efficient antidepressant treatment
Articolo in rivista - Review Essay
Transcription factors Role: BSU (Biological study unclassified); BIOL (Biological study) (CREB (cAMP-responsive element-binding); signaling pathways of cAMP protein kinase may involve in cAMP-responsive element binding protein regulating gene expression; neuroplasticity and implicated in mechanism of action of antidepressant); G proteins Role: BSU (Biological study unclassified); BIOL (Biological study) (calcium/calmodulin dependent kinase pathway may involve in activity dependent regulation of gene expression and implicated in mechanism of action of antidepressant); Gene expression; Signal transduction (signaling pathways of cAMP protein kinase; calcium/calmodulin dependent kinase; MAPK may involve in activity dependent regulation of gene expression and implicated in mechanism of action of antidepressant); Antidepressants; Brain; Synaptic plasticity (signaling pathways of cAMP protein kinase; calcium/calmodulin dependent kinase; MAPK may involve in activity dependent regulation of gene expression; neuroplasticity and implicated in mechanism of action of antidepressant);
English
115
134
20
Tardito, D., Perez, J., Tiraboschi, E., Musazzi, L., Racagni, G., Popoli, M. (2006). Signaling pathways regulating gene expression, neuroplasticity, and neurotrophic mechanisms in the action of antidepressants : a critical overview. PHARMACOLOGICAL REVIEWS, 58(1), 115-134 [10.1124/pr.58.1.7].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/278415
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