Research
Neuronal chaperones and proteasomal sorting in Motor Neurone Disease
Reference Code: Cheetham/Oct05/6213Grantee: Prof M Cheetham
Grantee Institution: Institute of Opthalmology, University College London
Duration: 3 years
Amount: £73,000 (MND Association Prize Studentship)
Description:
What this research means to you: In MND, damaged motor neurones contain "clumps" of proteins (known as aggregates) that get in the way of normal processes. This project will investigate two proteins found in nerve cells that may be able to limit the formation of these aggregates. If manipulation of the proteins can be shown to slow disease progression in a model of MND, treatments aimed at enhancing their activity could be developed in the future.
The researcher explains in detail: “Our studies of two proteins, HSJ1a and HSJ1b belonging to a group of proteins known as ‘neuronal chaperones’, in laboratory models of MND have shown that they promote the normal degradation of proteins by machinery within the cell known as the proteasome and that HSJ1a & HSJ1b are cytoprotective. A classical sign in motor neurones affected by MND is the accumulation of proteins within the cell, known as aggregation. Thus the potential relevance of HSJ1a & HSJ1b to MND is their ability to suppress aggregation and other cellular signs of disease. In this project we wish to test the effect that these neuronal chaperone proteins have on protein aggregation and proteasome function. In particular, the student, Wendy Mustill, will examine the ability of HSJ1 proteins to modulate the aggregation of mutant SOD1 in a cell culture model. Wendy will then progress to investigate the effects of manipulating HSJ1 in a model of MND (SOD1 G93A). HSJ1 levels will be altered by genetic modification and pharmacological treatment to test if HSJ1 can be used to slow disease progression. Demonstration that HSJ1 can be used to slow MND progression will set the scene for future studies that could lead to patient treatments based on enhancing HSJ1 function.”
Related abstracts:
HSJ1 is a neuronal shuttling factor for the sorting of chaperone clients to the proteasome.
