Timö Myöhänen
PREP in Neurodegenerative Disorders Group
Helsinki, Finland
Website

Program

"PREP as a drug target for neurodegenerative diseases – from failure to bright future?"

Prolyl oligopeptidase (PREP, POP) is a serine protease that has been studied in the context of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, since 1980s. PREP enzymatic activity was found to be elevated in post mortem tissues of Alzheimer’s patients, and the levels of several putative PREP substrates contributing to memory and cognition were found to be decreased. This led to development of small-molecular PREP inhibitors that showed promising results in preclinical memory models but after several phase 1 studies, the PREP inhibitor development was diminished. 

New era for PREP research started in 2008, when Brandt et al. published a study describing that PREP accelerates the aggregation of alpha-synuclein, the potential key pathological driver for Parkinson’s disease. After the finding, my team has shown that small-molecular PREP ligand can reduce alpha-synuclein aggregation and toxicity in different Parkinson’s disease models, and similar effect is also seen with Tau, the main component of neurofibrillary tangles seen in Alzheimer’s disease and other dementias. The most recent findings indicate that PREP inhibition might not be needed for these actions, but modification of PREP conformation may be the key for disease-modifying effects in neurodegenerative diseases.

Host: Roland HELLINGER

Contact for questions: Helmut KUBISTA