Alzheimer's disease (AD) is the most common form of dementia worldwide. β-amyloid peptide (Aβ) is currently assumed to be the main cause of synaptic dysfunction and cognitive impairments in AD, but the molecular signaling pathways underlying its neurotoxic consequences have not yet been completely explored. Additional investigations regarding these pathways will contribute to development of new therapeutic targets. In context, developing evidence suggest that Aβ decreases brain-derived neurotrophic factor (BDNF) mostly by lowering phosphorylated cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) protein. In fact, it has been observed that brain or serum levels of BDNF appear to be beneficial markers for cognitive condition. In addition, the participation of transcription mediated by CREB has been widely analyzed in the memory process and AD development. Designing pharmacologic or genetic therapeutic approaches based on the targeting of CREB-BDNF signaling could be a promising treatment potential for AD. In this review, we summarize data demonstrating the role of CREB-BDNF signaling pathway in cognitive status and mediation of Aβ toxicity in AD. Finally, we also focus on the developing intervention methods for improvement of cognitive decline in AD based on targeting of CREB-BDNF pathway.

中文翻译：

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CREB ​​和 BDNF 在神经生物学和阿尔茨海默病治疗中的作用

阿尔茨海默病 (AD) 是全世界最常见的痴呆症。 β-淀粉样肽（Aβ）目前被认为是 AD 突触功能障碍和认知障碍的主要原因，但其神经毒性后果背后的分子信号传导途径尚未完全探索。关于这些途径的额外研究将有助于开发新的治疗靶点。在这方面，越来越多的证据表明，Aβ 主要通过降低磷酸化环磷酸腺苷 (cAMP) 反应元件结合蛋白 (CREB) 蛋白来降低脑源性神经营养因子 (BDNF)。事实上，据观察，大脑或血清中的 BDNF 水平似乎是认知状况的有益标志。此外，CREB介导的转录在记忆过程和AD发展中的参与已被广泛分析。基于 CREB-BDNF 信号传导靶向设计药理学或基因治疗方法可能是 AD 的一种有前景的治疗潜力。在这篇综述中，我们总结了证明 CREB-BDNF 信号通路在 AD 认知状态和 Aβ 毒性介导中的作用的数据。最后，我们还重点开发基于CREB-BDNF通路靶向的改善AD认知衰退的干预方法。