Unravelling the role of prolyl-hydroxylase domain proteins (PHDs) in MND

Description:

What this research means to you: A family of proteins known as PHDs have been linked to a number of the mechanisms contributing to motor neurone degeneration in MND. This project aims to establish whether the PHDs really are involved in the disease process and if so, whether manipulation of these proteins could provide a future treatment strategy.

The researcher explains in more detail: Our research group was responsible for the discovery of a link between a deficiency in Vascular Endothelial Growth Factor (VEGF) and motor neurone degeneration. Normally, more VEGF is made in response to low oxygen levels in the body. The Prolyl-hydroxylase domain proteins (PHDs) act as oxygen sensors in cells and control how much VEGF is manufactured. The PHDs are therefore postulated to play a role in neurodegeneration associated with VEGF deficiency.
More recently, we have shown that PHDs are also involved in protecting cells against oxidative stress and in regulating the function of mitochondria (the cell’s “batteries”). Oxidative stress and mitochondrial dysfunction are important features of diseased neurones in MND, so this further implicates problems with PHDs in the disease process.
This project aims to further investigate the link between PHDs and MND by altering the levels of PHDs in mice that model the disease. If PHDs do affect motor neurone degeneration, we will then examine whether chemicals that already exist to alter the action of PHDs have potential as treatments for MND.