PREP lab

Dissertation of Henri Pätsi is on! Looking forward to a nice discussion with Prof. Pieter van der Veken from University or Antwerp, Belgium.

PhD dissertation #6 from the PREP lab is approaching as Henri Pätsi will defend his PhD thesis entitled "Non-Peptidic Modulators of the Protein-Protein Interaction-Mediated Functions of Prolyl Oligopeptidase" on Saturday Oct 7th! Prof. Pieter van der Veken from University of Antwerp, Belgium, will serve as the opponent. Check the link for further details!

Henri Pätsi: Non-Peptidic Modulators of the Protein-Protein Interaction-Mediated Functions of Prolyl Oligopeptidase

Our latest publication was accepted in the Journal of Medicinal Chemistry! We have shown earlier that a reference PREP inhibitor, KYP-2047, has good efficacy in various alpha-synuclein based Parkinson's disease models. However, KYP-2047 is good reference but non-patentable, and having very little possibilities for further drug development.

In this paper, we describe a family of completely novel structure and family of PREP inhibitors, that are equally effective to KYP-2047 in alpha-synuclein-based mouse models (having disease-modifying effect). Great collaboration between our medicinal chemistry and pharmacology teams - and more to come!

Nonpeptidic Oxazole-Based Prolyl Oligopeptidase Ligands with Disease-Modifying Effects on α-Synuclein Mouse Models of Parkinson’s Disease Prolyl oligopeptidase (PREP) is a widely distributed serine protease in the human body cleaving proline-containing peptides; however, recent studies suggest that its effects on pathogenic processes underlying neurodegeneration are derived from direct protein–protein interactions (PPIs) and not fro...

It’s on! PhD dissertation of M.Sc. Tony Eteläinen from PREP lab. Looking forward to interesting discussion with the opponent, Prof. Heikki Tanila from Itä-Suomen yliopisto - University of Eastern Finland (UEF)

We are extremely pleased to share that our recent manuscript got published in Science Translational Medicine! In this study, we show from protein level to frontotemporal dementia (FTD) mouse model that PREP inhibition reduces Tau aggregation via direct interaction, and also via protein phosphatase 2A activation and autophagy. In the FTD-mouse, this led to disease-modifying effect and restoration of normal cognitive skills although the treatment was initiated by the time of symptom onset.

We want to acknowledge PREP lab members in University of Helsinki and University of Eastern Finland ( ), for this awesome work, and particulary my student and soon-to-be PhD Tony Eteläinen who made huge amout of work for the study. I'm also deeply grateful for Prof. Stephen Haggarty and Dr. Maria Catarina Silva, PhD for such a great collaboration with patient-derived cells.

Huge thanks to our long-term supporters Suomen Akatemia, , Business Finland and

A PREP inhibitor may help stop the progression of frontotemporal dementia Inhibition of the PREP enzyme was successful in stopping the progression of frontotemporal dementia in a mouse model of the disea. It also reduced the accumulation of Tau protein in neurons, which is typical of dementias.

Next Friday my 5th student from will defend PhD thesis, as M.Sc. Tony Eteläinen has his dissertation! Very excited to follow the discussion between Tony and his opponent, Prof. Heikki Tanila from University of Eastern Finland. Tony’s 3rd article for the thesis was just accepted (right in time) - more information about that will follow later this week 😉

Tony Eteläinen: The effect of prolyl oligopeptidase inhibition on protein aggregation and oxidative stress in the models of neurodegenerative diseases

Former PhD student of PREP lab, Dr. Tommi Kilpeläinen, received the best thesis award of Finnish Pharmacological Society in 2021! Huge congrats, Tommi!

Our team will be today and tomorrow at , presenting the NeuroPREP project. Come stop by if you are around!

NeuroPREP slows down the progression of neurodegenerative diseases | University of Helsinki Entirely novel compounds slow down or even halt the progression of Parkinson’s disease and Alzheimer's disease.

Although it has been quiet in PREP lab page, we have not been lazy. Check out our most recent paper at Neuropharmacology where we show that even if you reduce insoluble alpha-synuclein in mice (that should be toxic), it does not automatically protect the cells. Very nice work by Tony Eteläinen and Tommi Kilpeläinen!

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Very happy to get a 3-year grant from Sigrid Juselius Foundation! We can start building up our research in UEF!

1–3-year grants - Sigrid Jusélius Foundation Application period at 23:59. Target groups The 1-3-year grants are targeted for two target groups for medical research: Senior researchers […]

One more paper out for this year from PREP lab, this time to Biochemical Pharmacology! In this study by Hengjing Cui et al., we showed that PREP regulates not only macroautophagy but also chaperone-mediated autophagy and acts a link between these cellular recycling mechanisms.

This is also important for alpha-synuclein degradation as it can be cleaved via both autophagy mechanisms.

Prolyl oligopeptidase acts as a link between chaperone-mediated autophagy and macroautophagy The accumulation of aggregated α-synuclein (α-syn) has been identified as the primary component of Lewy bodies that are the pathological hallmarks of …