Collaborative paper accepted in Biomedicine & Pharmacotherapy

Our research paper authored in conjunction with researchers from Uppsala University and our own Faculty of Medicine was recently accepted in the journal Biomedicine & Pharmacotherapy. The research shows that inhibition of prolyl oligopeptidase (PREP) enhances the degradation of pre-formed alpha-synuclein (aSyn) fibrils in human neuroblastoma cells by a mechanism related to macroautophagy.

Full text of the open access article can be found here: https://www.sciencedirect.com/science/article/pii/S0753332220309811



Alpha-synuclein (aSyn) has been identified as a major factor in the development of Parkinson's disease (PD). Several forms of aSyn exits, including monomeric (singular), oligomeric (several grouped in one) and fibril-like forms. While all of these forms are found in the brains of PD patients, there is still debate on which of these forms is the most harmful one.



It has been shown by us and others that prolyl oligopeptidase PREP directly interacts with aSyn in non-enzymatic manner and increases its propensity to form oligomeric and fibril forms. Our earlier research has concluded that inhibition of aSyn with KYP-2047 decreases the amount of soluble oligomers. In this new research we show that the same effect exists for the larger, unsoluble fibrils as well. The results support our view of PREP inhibitors as a safe and effective way in treating neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases.