cdk5 signalling and disruption to the Golgi apparatus in amyotrophic lateral sclerosis

Description:

What this research means to you: Nerve cells contain various structures, all performing different functions. Some of these structures are damaged in MND. This project will concentrate on how a chemical called cdk5 may damage structures known as Golgi apparatus. Drugs that block the actions of this chemical are already being developed for other diseases, so this research may encourage the specific application of such drugs to MND.

The researcher explains in detail: “Two prominent pathological features that are seen in MND and mouse models of the disease are neurofilament accumulations and disruption to the Golgi apparatus. Neurofilaments are part of the “cytoskeleton” that determines the shape of neurones and the Golgi apparatus regulates the secretion of proteins from the cell. Understanding the mechanisms by which these pathologies arise is believed to be important since this is likely to reveal targets for drug intervention. Recently we have discovered that two chemicals in the same biochemical pathway, known as ‘cprk’ and ‘cdk5’, may have a possible role in neurofilament toxicity. Cprk has also been implicated in disrupting the function of the Golgi apparatus. Thus, the deregulation of this biochemical pathway in ALS may cause abnormal neurofilament accumulation, and disruption to the Golgi apparatus. The aim of this project is to study this latter possibility in more detail. Aside from MND, disruptions to similar biochemical pathways are seen in a variety of diseases including cancer and Alzheimer’s disease, and drugs that block these effects are being generated by the pharmaceutical industry as potential treatments for these disorders. Thus, understanding how cdk5 and cprk are involved in MND may facilitate the development of similar treatments for MND.”

This project is supported by The Grand Charity