The etiologies of Parkinson and Alzheimer’s diseases are still poorly understood and to date only very limited palliative treatment options exist. The accumulation of α-synuclein aggregates is the hallmark of Parkinson’s disease, and more generally of synucleinopathies. The accumulation of tau aggregates however is classically found in the brains of patients with dementia, and this type of neuropathological feature specifically defines the tauopathies. Tau and α-synuclein are both partially unfolded proteins that can form abnormal toxic oligomers and intracellular aggregates under pathological conditions. Furthermore, mutations in either are responsible for severe dominant familial neurodegeneration. Using bimolecular protein-fragment complementation, we developed a set of innovative assays to monitor in real time α-synuclein and tau abnormal polymerization in living cells. Additionally in an attempt of generating better in vitro models for neurodegeneration, we collected patient-derived fibroblasts to produce induced pluripotent stem cells (hiPSCs) that we subsequently redifferentiated into neurons. Using these tools we screened for oligomerization modulators.



Dr. Simon Moussaud, Institutionen för neurokemi, Stockholms universitet, simon.moussaud@neurochem.su.se