The role of CREB signaling in Alzheimer's disease and other cognitive disorders
The role of CREB signaling in Alzheimer's disease and other cognitive disorders
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DOI：
10.1515/rns.2011.018
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发表时间：
2011-04-01
影响因子：
4.1
通讯作者：
Valero, Jorge
中科院分区：
文献类型：
--
作者：
Saura, Carlos A.;Valero, Jorge
大脑中的基因表达变化影响正常和病理老化期间的认知。了解调节认知基因表达网络的细胞过程的进展与开发年龄相关认知障碍的治疗干预措施有关。介导记忆储存的突触功效需要激活由转录因子cAMP-反应元件结合蛋白（CREB）等调控的特定基因表达程序。CREB信号传导对于突触可塑性的长期变化至关重要，突触可塑性介导短期记忆向长期记忆的转换。CREB信号传导最近已经参与了包括认知和神经退行性疾病在内的几种脑病理状况。β-淀粉样蛋白（A β）肽在阿尔茨海默病的发病机制中起着至关重要的作用，它通过CREB信号通路改变了海马依赖性突触可塑性和记忆，并介导了突触丢失。改变的CREB信号传导与包括亨廷顿氏病和Rubinstein-Taybi和Coffin-Lowry综合征在内的其他认知障碍有关的事实表明CREB信号传导在认知功能障碍中的关键作用。在这篇综述中，我们总结了最近的研究结果表明CREB及其共激活因子CREB结合蛋白和CREB调节的转录共激活因子在认知过程中的作用，在正常和病理老化。我们还讨论了基于CREB靶向的新型治疗策略的发展，以改善衰老和认知障碍中的认知下降。
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 beta-amyloid (A beta) 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.