The role of CREB signaling in Alzheimer’s disease and other cognitive disorders
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Carlos A. Saura
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Jorge Valero
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.
©2011 by Walter de Gruyter Berlin New York
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Artikel in diesem Heft
- Imaging spatial learning in the brain using immediate early genes: insights, opportunities and limitations
- Silencing of CDK5 as potential therapy for Alzheimer’s disease
- The role of CREB signaling in Alzheimer’s disease and other cognitive disorders
- The positive impact of physical activity on cognition during adulthood: a review of underlying mechanisms, evidence and recommendations
- Representation of temporal sound features in the human auditory cortex
- Modulation of fear memory by retrieval and extinction: a clue for memory deconsolidation
- Adenosine 2A receptor: a crucial neuromodulator with bidirectional effect in neuroinflammation and brain injury
- Errata
- Anatomical reference frame versus planar analysis: implications for the kinematics of the rat hindlimb during locomotion
- Estradiol acts through nuclear- and membrane-initiated mechanisms to maintain a balance between GABAergic and glutamatergic signaling in the brain: implications for hormone replacement therapy
