The role of Wnt signalling in synaptic maintenance

Wnt 信号在突触维持中的作用

• 批准号: G0802241/1
• 负责人: Patricia Salinas
• 金额: $ 190.71万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0802241%2F1
• 关键词: role; Wnt; signalling; synaptic; maintenance

The formation of functional synapses, points of contact between two nerve cells (neurons) is crucial for proper brain function. Synapses are very dynamic structures that grow, shrink and change shape through the entire life of the organism. A dialogue between the pre-synaptic neuron (neurotransmitter releasing cell) and its postsynaptic target (a neurotransmitter responding cell) is essential for the formation, growth and maintenance of synapses. Importantly, the formation of new synapses and the remodelling of old ones underlay important functions such as learning and memory. Moreover, recent studies suggest that synaptic loss precedes the death of neurons observed in several neurodegenerative diseases. However, little is known about how synapses are maintained or protected against injury.Our laboratory has been studying the function of secreted factors, called Wnts, in the maintenance of synapses. We found that Wnt blockade induces the loss of mature synapses indicating that Wnts are critical for their maintenance. In this grant proposal, we will examine the molecular mechanism by which Wnts regulate synaptic maintenance and how this process influences neuronal connectivity and animal behaviour. Our results could contribute to the development of therapeutic strategies for the treatment of diseases in which synapses are compromised.

功能性突触的形成，即两个神经细胞（神经元）之间的接触点，对大脑的正常功能至关重要。突触是非常动态的结构，在生物体的整个生命过程中生长，收缩和改变形状。突触前神经元（神经递质释放细胞）与其突触后靶细胞（神经递质反应细胞）之间的对话对于突触的形成、生长和维持至关重要。重要的是，新突触的形成和旧突触的重塑是学习和记忆等重要功能的基础。此外，最近的研究表明，在几种神经退行性疾病中观察到的神经元死亡之前突触丧失。然而，突触是如何维持或保护免受损伤的，我们的实验室一直在研究分泌因子，称为Wnts，在突触维持中的功能。我们发现Wnt阻断诱导成熟突触的丧失，表明Wnt对于它们的维持至关重要。在这项资助提案中，我们将研究Wnt调节突触维持的分子机制以及这一过程如何影响神经元连接和动物行为。我们的研究结果可能有助于开发治疗突触受损疾病的治疗策略。