Role of Wnt Signaling in the Control of Adult Hippocampal Functioning in Health and Disease: Therapeutic Implications
Role of Wnt Signaling in the Control of Adult Hippocampal Functioning in Health and Disease: Therapeutic Implications
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DOI：
10.2174/1570159x11311050001
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发表时间：
2013-09-01
影响因子：
5.3
通讯作者：
Arias, Clorinda
中科院分区：
文献类型：
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作者：
Ortiz-Matamoros, Abril;Salcedo-Tello, Pamela;Arias, Clorinda
Wnt信号通路在神经元的成熟、迁移、连接和突触形成等发育过程中发挥重要作用。越来越多的证据也表明其在成熟脑中的功能，其中与轴突重塑、树突生长、突触活动、神经发生和行为可塑性的调节有关。Wnt信号通路参与的蛋白质在成年海马中有表达，提示Wnt信号通路在海马的功能中起着终生的作用。事实上，Wnt配体局部作用以调节神经发生、神经元细胞形状和突触前和突触后组装，这些事件被认为是与长时程增强和认知任务（如学习和记忆）相关的突触功能变化的基础。最近的数据表明，阿尔茨海默病（AD）患者脑中Wnt拮抗剂Dickkopf-1（DKK 1）的表达增加，表明Wnt信号传导功能障碍也可能导致AD病理学。我们在这里审查Wnt相关分子的表达与成人大脑中的生理和病理海马功能的证据。Wnt相关机制的基本方面海马可塑性以及海马功能障碍可能依赖于Wnt失调的证据进行了分析。这些信息将为开发与异常脑可塑性相关的神经退行性疾病的治疗方法提供一些可能的治疗靶点的线索。
It is well recognized the role of the Wnt pathway in many developmental processes such as neuronal maturation, migration, neuronal connectivity and synaptic formation. Growing evidence is also demonstrating its function in the mature brain where is associated with modulation of axonal remodeling, dendrite outgrowth, synaptic activity, neurogenesis and behavioral plasticity. Proteins involved in Wnt signaling have been found expressed in the adult hippocampus suggesting that Wnt pathway plays a role in the hippocampal function through life. Indeed, Wnt ligands act locally to regulate neurogenesis, neuronal cell shape and pre- and postsynaptic assembly, events that are thought to underlie changes in synaptic function associated with long-term potentiation and with cognitive tasks such as learning and memory. Recent data have demonstrated the increased expression of the Wnt antagonist Dickkopf-1 (DKK1) in brains of Alzheimer's disease (AD) patients suggesting that dysfunction of Wnt signaling could also contribute to AD pathology. We review here evidence of Wnt-associated molecules expression linked to physiological and pathological hippocampal functioning in the adult brain. The basic aspects of Wnt-related mechanisms underlying hippocampal plasticity as well as evidence of how hippocampal dysfunction may rely on Wnt dysregulation is analyzed. This information would provide some clues about the possible therapeutic targets for developing treatments for neurodegenerative diseases associated with aberrant brain plasticity.