Overview
One hallmark of neurodegenerative diseases is the formation of protein aggregates, such as beta-amyloid plaques in AD, Lewy bodies in PD, and nuclear inclusions in HD. Their roles remain unclear and it is debated whether they are a cause, a consequence or an epiphenomenon in the neurodegenerative process. The NCoE is studying the formation, clearance and toxicity of these aggregates, and their roles in neurodegeneration.
The NCoE has access to clinical, population-based and neuropathologically confirmed cohorts of patients with neurodegenerative diseases and uses biomaterial from a brain bank, cerebrospinal fluid repositories and blood samples to examine markers of neuronal dysfunction and cellular stress. The NCoE studies each functional change in many different disease models, which may reveal common underlying mechanisms. This is revolutionary, since traditional research in neurodegenerative diseases seldom crosses disease boundaries.
Cellular stress encompasses molecular events that precede neuronal death, such as mitochondrial dysfunction, endoplasmic reticulum stress, excitotoxicity, DNA changes, nitric oxide toxicity and inflammation. These events either contribute to the degenerative process itself or to the adaptive processes in which the neurons attempt to survive an insult. Understanding cellular stress in the nervous system may both clarify pathogenic mechanisms and reveal novel therapeutic targets. Neuronal dysfunction starts long before cell death in HD, PD and AD. This has become clear from animal models, and also clinical symptoms appear to correlate better with synaptic dysfunction than with neuronal loss.
A major unmet medical need for AD, HD and PD is disease-modifying therapies. We use a case-control brain bank and the exciting opportunity to perform genetic screens for novel targets. We have different types of drug screens and a wide range of disease models to validate new drug candidates. Discovery of novel biomarkers that allow monitoring of disease progression are also key objectives that will facilitate the development of novel therapies.
As a new approach for synergy creation and integration of different high-level Nordic laboratories, the NCoE is running a strong scientific training program that brings together students, post-docs and supervisors from all Work Packages. It includes specialized technical workshops where research methods and reagents are shared between the groups as well as other workshops devoted to specific general skills needed as a scientist. Technical platforms within the NCoE are freely available to all partners.