Linking brain pathologies to ion balance
Understanding what causes TSEs and how disease progression leads to severe neurodegeneration are key steps towards development of innovative treatments for these diseases. TSEs are caused by protein-like pathogens called prions (PrPs). PrPs are naturally produced by human neuronal cells (termed PrPC), however, their pathogenic counterparts are mutated forms which can infect the brain and result in widespread nerve cell death. Following the widespread effects of the BSE epidemic in cattle across Europe, the EU sought to examine the molecular basis of TSEs in a number of species, including humans. The EU-funded PRP AND NEURODEGENER project, under the auspices of the LIFE QUALITY programme, set out to closely examine the links between PrP infection and neurodegeneration. A main point of focus was the effect of PrP infection on ion transport and balance in brain cells, and whether ion imbalances played a role in the onset of neurodegeneration. More specifically, project partners worked on elucidating the role of PrPC in copper ion transport across cell membranes. Although PrPC expression in cells was correlated to copper binding, PrPC involvement in copper transport could not be supported. Copper can be extremely toxic as well as beneficial to cell stability depending on the concentration of copper ions. Therefore maintaining a proper balance is extremely important at a molecular level. PrPC could be playing a role in protecting cells from excessive copper ion concentrations as indicated by experimental studies. Supporting this line of research is likely to yield important new insights into the role of PrPC in brain physiology, thus paving the way for a greater understanding of TSE-related pathologies. The financial impact of these studies could be significant, given the global interest in TSE occurrence, especially in cattle populations.
