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Reviews in the Neurosciences

Editor-in-Chief: Huston, Joseph P.

Editorial Board Member: Topic, Bianca / Adeli, Hojjat / Buzsaki, Gyorgy / Crawley, Jacqueline / Crow, Tim / Eichenbaum, Howard / Gold, Paul / Holsboer, Florian / Korth, Carsten / Lubec, Gert / McEwen, Bruce / Pan, Weihong / Pletnikov, Mikhail / Robbins, Trevor / Schnitzler, Alfons / Stevens, Charles / Steward, Oswald / Trojanowski, John

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increased IMPACT FACTOR 2013: 3.314
Rank 105 out of 251 in category Neurosciences in the 2013 Thomson Reuters Journal Citation Report/Science Edition

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The role of CREB signaling in Alzheimer’s disease and other cognitive disorders

1 / Jorge Valero1

1Institut de Neurociències, Departament Bioquímica i Biologia Molecular, Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Universitat Autònoma de Barcelona, E-08193 Bellaterra, Spain

Corresponding author

Citation Information: Reviews in the Neurosciences. Volume 22, Issue 2, Pages 153–169, ISSN (Online) 2191-0200, ISSN (Print) 0334-1763, DOI: 10.1515/rns.2011.018, April 2011

Publication History

Published Online:
2011-04-12

Abstract

Gene expression changes in the brain affect cognition during normal and pathological aging. Progress in understanding the cellular processes regulating gene expression networks in cognition is relevant to develop therapeutic interventions for age-related cognitive disorders. Synaptic efficacy mediating memory storage requires the activation of specific gene expression programs regulated, among others, by the transcription factor cAMP-response element binding protein (CREB). CREB signaling is essential for long-lasting changes in synaptic plasticity that mediates the conversion of short-term memory to long-term memory. CREB signaling has been recently involved in several brain pathological conditions including cognitive and neurodegenerative disorders. The β-amyloid (Aβ) peptide, which plays a crucial role in the pathogenesis of Alzheimer’s disease, alters hippocampal-dependent synaptic plasticity and memory and mediates synapse loss through the CREB signaling pathway. The fact that altered CREB signaling has been implicated in other cognitive disorders including Huntington’s disease and Rubinstein-Taybi and Coffin-Lowry syndromes suggests a crucial role of CREB signaling in cognitive dysfunction. In this review paper, we summarize recent findings indicating a role of CREB and its coactivators CREB binding protein and CREB-regulated transcription coactivator in cognition during normal and pathological aging. We also discuss the development of novel therapeutic strategies based on CREB targeting to ameliorate cognitive decline in aging and cognitive disorders.

Keywords: aging; Alzheimer’s disease; amyloid; cAMP-response element binding protein (CREB); CREB-regulated transcription coactivator (CRTC); dementia; gene expression; Huntington’s disease; neurodegeneration

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