Endogenous inhibition of CaMKII: A Novel molecular mechanism to terminate memory formation

CaMKII 的内源性抑制：终止记忆形成的新分子机制

• 批准号: G0800393/1
• 负责人: Karl Giese
• 金额: $ 58.64万
• 依托单位: King's 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=G0800393%2F1
• 关键词: Endogenous; inhibition; CaMKII; Novel; molecular

What mechanisms are needed to make and store memories in the brain? These mechanisms are still not sufficiently well understood, a fact that prevents us from curing learning and memory deficits in diseases such as mental retardation. My laboratory is studying mechanisms that underlie learning and memory in mice. We perform studies with mice, because in humans we cannot perform well-defined experimental manipulations that are needed to establish mechanisms, and mice are the closest animal species to humans for which a very large repertoire of sophisticated manipulations has been established. We and others have shown that an enzyme called CaMKII is required for the making, but not for the storage, of memory. To terminate the memory making the enzyme needs to be switched off. We have proposed that an endogenous inhibitor protein (CaMKIINalpha) performs this function. More studies are required to validate our hypothesis and here we propose to carry out such studies. If our hypothesis were correct, then follow-up studies will examine whether the novel memory mechanism could be impaired in diseases with associated memory deficits.

大脑中需要什么机制来制造和储存记忆？这些机制仍然没有得到充分的理解，这一事实阻碍了我们治愈智力迟钝等疾病的学习和记忆缺陷。我的实验室正在研究老鼠学习和记忆的机制。我们用小鼠进行研究，因为在人类中，我们不能进行建立机制所需的明确的实验操作，而小鼠是最接近人类的动物物种，已经建立了非常大的复杂操作库。我们和其他人已经证明，一种名为CaMKII的酶是制造记忆所必需的，而不是储存记忆。为了终止记忆的产生，需要关闭酶。我们已经提出，内源性抑制蛋白（CaMKIIN α）执行这一功能。需要更多的研究来验证我们的假设，在这里，我们建议进行这样的研究。如果我们的假设是正确的，那么后续研究将检查这种新的记忆机制是否会在伴有记忆缺陷的疾病中受损。