Harnessing the heat shock response as a neuroprotective strategy in models of motor neurone disease

Reference Code: Greensmith/Oct05/6211
Grantee: Dr L Greensmith
Grantee Institution: Institute of Neurology, University College London
Duration: 3 years
Amount: £72,400 (MND Association Prize Studentship)

Description:

What this research means to you: This project will investigate a cellular defence mechanism that may help prolong the life of motor neurones. By studying the way that this mechanism works to protect nerve cells, the researchers hope to learn how it can be exploited, potentially leading to the development of treatments for MND.

The researcher explains in detail: “In our laboratory we have been examining the role of ‘heat shock proteins’ (hsps) in the selective degeneration of motor neurons in MND. Levels of these Hsps are raised in all cells following periods of stress, where they promote cell survival. Hsps form part of cellular defence pathway, and act to prevent accumulation of damaged proteins, as well as directly interfering with cell death pathways. In the SOD1 mouse model of MND, we have recently shown that a novel compound called arimoclomol can induce motor neurons to activate Hsps and the cellular defence pathway, but only in cells under conditions of stress. In SOD1 mice, arimoclomol was found to significantly delay disease progression and increase lifespan. This was observed even when treatment was initiated after the onset of symptoms. However the precise mechanism by which higher levels of hsps protect cells in MND, remains unclear. In this project we plan to investigate the precise mechanism and site of action of hsps in order to optimise the exploitation of this cellular defence pathway in developing potential therapies for MND. We hope that the information obtained from the proposed experiments will allow us to optimise targeting of the heat shock defence pathway to either specific cell populations or intracellular pathways. This project will offer what we feel is an excellent training for students interested in MND, taking both a cellular and systems approach, and using a wide variety of techniques.”