Neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, are progressive diseases where neuronal death in brain causes clinical symptons like memory loss or movement disorders. Current drug therapies cannot stop or even delay neurodegeneration, and this leads to more and more severe symptoms as the disease progressess. It is not known what causes neuronal death in the first place but common toxic factor for several neurodegenerative diseases is abnormal protein accumulation that harms neurons in several ways.
Our studies have revealed that prolyl oligopeptidase, PREP, is one factor to induce protein accumulation, and importantly, this can be blocked by small-molecule PREP inhibitors. Our research is focused on understanding the mechanisms of how PREP increases the accumulation of protein accumulation - particularly alpha-synuclein and Tau, and studying if PREP inhibitors are effective in preventing the aggregation-prone protein accumulation and dissolve the surplus of protein aggregates from cells via enhanced autophagy. Another important aim is to find the best PREP inhibitor compounds to stop neurodegenerative diseases.