PFF induced striatal neurodegeneration model for preclinical proof of concept studies targeting alpha‐synuclein pathology

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder with more than half of the patients developing dementia about 10 years later, and is characterized by the accumulation of alpha‐synuclein protein aggregates in the PD brain. These inclusions, also called Lewy bodies, accompanied with the degeneration of dopaminergic neurons are the neuropathological hallmark of this devastating incurable disease. Currently a lot of effort is put in studying the involvement of different forms of alpha‐synuclein, i.e. monomeric, oligomeric, fibrillar and aggregated forms or different post translational modifications of the protein, and their contribution to disease progression. Targeting alpha‐synuclein might thus be of potential therapeutic value. Since the research field lacks good and consistent animal models for preclinical research, we’ve set up a mouse model based on the striatal administration of sonicated preformed fibrils (PFF).