Protein kinase N signalling and neurodegeneration in ALS

Description:

What this research means to you: This project will investigate whether a particular enzyme found in nerve cells becomes over-active in MND and causes some of the damage seen in diseased motor neurones. If this is the case, drugs can be developed to target the enzyme and keep it under control so that its ability to cause damage is limited.

The researcher explains the detail: “A pathological hallmark of MND is accumulations of neurofilaments in affected motor neurones. Neurofilaments are made in cell bodies of neurones and then transported down the nerve cell. It is generally believed that they accumulate in MND because they are not being transported properly. Neurofilaments are modified by addition of phosphate and the enzymes that do this are called kinases. We have shown that kinases slow down neurofilament transport and cause accumulation, similar to that seen in MND. Recently, a new neurofilament kinase has been identified called protein kinase N (PKN) and several studies have shown that it can be activated by a variety of pathological stimuli. This project aims to determine whether toxic insults associated with MND do indeed activate PKN and, if so, whether activated PKN disrupts neurofilament transport. If so, then the study will highlight the PKN pathway as a target for therapeutic intervention.”