The roles of FMRP in cortical development

FMRP 在皮质发育中的作用

• 批准号: G0601584/1
• 负责人: Peter Kind
• 金额: $ 55.62万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0601584%2F1
• 关键词: roles; FMRP; cortical; development

Fragile X syndrome is the most common form of mental retardation that can be inherited from ones? parents. It is caused by the absence of a single protein called the fragile X mental retardation protein or FMRP. Many of the severe cognitive symptoms of fragile X are associated with abnormal organization of the cerebral cortex, the region of the brain that is primarily responsible for mediating conscious sensory experiences, thoughts and actions.Since the symptoms of fragile X syndrome first appear during childhood development it is likely that establishing how FMRP influences development of the brain will lead to a better understanding of fragile X syndrome and may suggest new or improved treatments. However, while most scientific investigations of FMRP have focused on its role in adults, very little attention has been given to the role of FMRP in the development of the cerebral cortex. We propose to address this issue by establishing where in the cerebral cortex FMRP is found during different stages of development and by determining how removal of FMRP, as occurs in FXS, influences the development and organization of the cerebral cortex.The most promising framework established so far for designing treatments for fragile X syndrome is based on a recent theory which suggests that FMRP restricts neuronal communication by altering the function of a neurotransmitter receptor, called mGluR. The second part of our study will focus on how FMRP and mGluRs interact during development. We will carry out experiments that will establish if FMRP and mGluR5 interact during development and will determine if these interactions support the mGluR theory of fragile X syndrome.Since the genetic factors that underlie the organizational development of the cerebral cortex are only beginning to be established, elucidation of the roles of FMRP in these processes will represent a significant contribution to understanding the mechanisms involved in development of the cerebral cortex. Moreover, our experiments will provide fundamental insights into the cellular mechanisms through which the altered brain function in fragile X patients arise and therefore may be important for discovery of new therapeutic treatments for mental retardation.

脆性X染色体综合征是一种最常见的智力迟钝，可以遗传给孩子。的父母。它是由缺乏一种叫做脆性X智力迟钝蛋白或FMRP的蛋白质引起的。脆性X染色体患者的许多严重认知症状都与大脑皮层的异常组织有关，大脑皮层主要负责调节有意识的感官体验、思想和行为。由于脆性X综合征的症状首先出现在儿童发育期间，因此确定FMRP如何影响大脑发育可能会导致对脆性X综合征的更好理解，并可能提出新的或改进的治疗方法。然而，虽然大多数关于FMRP的科学研究都集中在它在成人中的作用，但很少有人关注FMRP在大脑皮层发育中的作用。我们建议通过确定大脑皮层在不同发育阶段发现FMRP的位置，以及确定FMRP的去除如何影响大脑皮层的发育和组织来解决这个问题。迄今为止，最具前景的设计脆性X综合征治疗方案的框架是基于最近的一项理论，该理论认为FMRP通过改变一种叫做mGluR的神经递质受体的功能来限制神经元间的交流。我们研究的第二部分将关注FMRP和mGluRs在发育过程中的相互作用。我们将开展实验，以确定FMRP和mGluR5是否在发育过程中相互作用，并确定这些相互作用是否支持脆性X综合征的mGluR理论。由于大脑皮层组织发育的遗传因素才刚刚开始确立，阐明FMRP在这些过程中的作用将对理解大脑皮层发育的机制做出重大贡献。此外，我们的实验将为脆性X患者大脑功能改变的细胞机制提供基本见解，因此可能对发现新的治疗智力迟钝的治疗方法很重要。