Dr Thimo Kurz, University of Glasgow
Professor Michael Glickman, Technion - Israel Institute of Technology
Alzheimer's Disease is the most common type of neurodegeneration and because it affects the brain causes progressive cognitive decline. The brains of Alzheimer patients contain protein clumps, which are thought to cause the disease by taxing nerve cells and leading to their death. Protein clumps are caused by inevitable damage that afflicts proteins over time. Healthy cells have the capacity to remove damaged proteins through multiple mechanisms that act in parallel as a safeguard. Sometimes these clearing mechanisms fail, causing slow build up of clumped proteins. Oddly enough, components of the clearing mechanisms are found in the clumps as well, indicating a snowball effect. Other than a few rare inherited cases, there is no good predictor for Alzheimer's, which often appears to inflict people sporadically. Nevertheless, as many are not affected, it is unclear what are the possible environmental and genetic reasons that put people at risk. Interestingly, a damaged form of a key clearing factor, called UBB+1, is prevalent in characteristic Alzheimer clumps, suggesting it may lead to disease.
The aim of this collaborative research is to understand the causative link between UBB+1 and Alzheimer's disease. Dr Kurz and Professor Glickman want to understand if UBB+1 is a risk factor for the development of sporadic Alzheimer's and if so, how it interferes with the healthy clearing mechanism of toxic protein clumps. What makes it appear sporadically is an enigma, which we aim to tackle by recreating the proper environmental and tissue context in the laboratory. We also plan to devise ways to block the formation of UBB+1 in neurons, to understand if this can stave off Alzheimer's disease. With this work we hope to lay the foundation for future curative, regenerative and preventative measures. In the long run, this may lead to new therapies for Alzheimer's Disease to improve the prognosis of affected individuals.
This collaboration brings together two teams from Israel and Scotland dedicated to solving how protein damage causes disease. The Glickman group at the Technion has the expertise for growing nerve cells, while the Kurz group at the University of Glasgow has experience with generating and analyzing mouse models.