MRC Transition Support Award [CDA] [Maria Jimenez-Sanchez]

MRC 过渡支持奖 [CDA] [Maria Jimenez-Sanchez]

基本信息

批准号：
MR/V036947/1
负责人：
Maria Jimenez-Sanchez
金额：
$ 55.69万
依托单位：
King's College London
依托单位国家：
英国
项目类别：
Fellowship
财政年份：
2022
资助国家：
英国
起止时间：
2022 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FV036947%2F1
关键词：
MRC Transition Support Award CDA

项目摘要

Drug discovery strategies have traditionally focused on neurons as the main targets in Alzheimer's disease and other brain disorders. In the brain, neurons are responsible for processing information, learning and memory, while other specialised brain cells called glial cells are necessary to maintain neuron health and to aid their function. To design effective therapeutic strategies for Alzheimer's disease, not only do we need to investigate how neurons become dysfunctional but also we need to better understand the contribution of glial cells to disease progression. The aim of my Career Development Award is to investigate how astrocytes, the most abundant type of glial cell, can protect neurons in Alzheimer's disease. We plan to identify some of the factors released from astrocytes that mediate neuroprotection, and with this information we will be able to design new and effective therapies. Our current research has led to novel and exciting discoveries that identified factors released from astrocytes exposed to conditions similar to those in Alzheimer's disease brain. These factors are known as chaperones, and they help to prevent the accumulation of abnormal proteins in the brain. What is even more interesting is that neurons can take up the chaperones released by astrocytes, perhaps in an attempt to protect the neurons.This Transition Support Award will enable my group to expand on our exciting findings and explore the potential neuroprotective effects of mimicking chaperone release from astrocytes. In Alzheimer's disease, tau protein builds up and forms clumps inside neurons. This proposal will explore the potential benefits of increasing astrocyte-released factors as a potential therapy to prevent tau clumps from forming. We will do this by delivering chaperones to slices of mouse brain, in which we will promote tau accumulation to mimic Alzheimer's disease brain. To further ensure that our findings are relevant to human disease, we will examine these chaperones in the spaces outside cells in post-mortem brain donated by people with Alzheimer's disease, as well as in cerebrospinal fluid from people living with Alzheimer's disease. I am a dementia researcher who is dedicated to building and consolidating my career as an independent group leader. This Award will enable me to expand my novel avenue of research and my findings will have a significant impact on our understanding of Alzheimer's disease and related disorders, as well as providing new directions for therapies.

药物发现策略传统上关注神经元，将其作为阿尔茨海默病和其他脑部疾病的主要靶标。在大脑中，神经元负责处理信息、学习和记忆，而其他称为神经胶质细胞的特殊脑细胞对于维持神经元健康并帮助其发挥功能是必需的。为了设计有效的阿尔茨海默病治疗策略，我们不仅需要研究神经元如何变得功能失调，还需要更好地了解神经胶质细胞对疾病进展的贡献。我的职业发展奖的目的是研究星形胶质细胞（最丰富的神经胶质细胞类型）如何保护阿尔茨海默病的神经元。我们计划确定星形胶质细胞释放的一些介导神经保护的因子，利用这些信息，我们将能够设计新的有效疗法。我们目前的研究取得了令人兴奋的新发现，确定了星形胶质细胞在暴露于与阿尔茨海默氏病大脑相似的条件下时释放的因子。这些因子被称为伴侣，它们有助于防止大脑中异常蛋白质的积累。更有趣的是，神经元可以吸收星形胶质细胞释放的伴侣，也许是为了保护神经元。这个过渡支持奖将使我的团队能够扩展我们令人兴奋的发现，并探索模仿伴侣释放的潜在神经保护作用来自星形胶质细胞。在阿尔茨海默病中，tau 蛋白在神经元内积聚并形成团块。该提案将探讨增加星形胶质细胞释放因子作为预防 tau 蛋白团块形成的潜在疗法的潜在益处。我们将通过向小鼠大脑切片提供伴侣来实现这一目标，其中我们将促进 tau 蛋白的积累，以模拟阿尔茨海默病的大脑。为了进一步确保我们的发现与人类疾病相关，我们将在阿尔茨海默病患者死后捐赠的大脑细胞外的空间以及阿尔茨海默病患者的脑脊液中检查这些伴侣。我是一名痴呆症研究员，致力于建立和巩固我作为独立小组领导者的职业生涯。该奖项将使我能够拓展我的新研究途径，我的发现将对我们对阿尔茨海默病和相关疾病的理解产生重大影响，并为治疗提供新的方向。