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

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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.