Finally, we got our studies on rotenone-induced alpha-synuclein aggregation, and the effect of PREP inhibition on this, published. This project started already at 2011 , and the original aim was to use rotenone toxin model in mice and then treat the animals with a PREP inhibitor. Now published cellular data was supposed to be just a supporting data for animal results. However, the animal model turned out to be unrepeatable, and we got the results only from our cellular models.

In brief, PREP inhibition by KYP-2047 significantly improved the cell viability of alpha-synuclein overexpressing cells when stressed by rotenone. Moreover, this was not an antioxidant effect but the effect of reduced alpha-synuclein aggregation process. Full-text article is available in the Neuroscience Letters website until 17th of November.

Usually in science it is good to collaborate. This time it was even better since we got two really good publications; one to PloSOne and other to Proceedings of National Academy of Sciences USA (PNAS). In PloSOne publication, group leader Timo Myöhänen was performing his specialty, immunohistochemistry, for Professor Pirkko Vihko’s group in a paper “Mice deficient in transmembrane prostatic acid phosphatase display increased GABAergic transmission and neurological alterations”.

Mari Savolainen and Timo Myöhänen participated on a study by Professor Sabrina Diano (Yale University School of Medicine), where the role of PREP on insulin and glucagon regulation was revealed. Our group members provided PREP plasmids that were used in the study. This paper was published in a very valued PNAS publication series.

Our manuscript, titled “The beneficial effect of a prolyl oligopeptidase inhibitor, KYP-2047, on alpha-synuclein clearance and autophagy in A30P transgenic mouse“, got accepted for publication to Neurobiology of Disease (impact factor 5.642). In this paper, we showed that PREP inhibition reduced specifically the toxic species of alpha-synuclein, high-molecular weight oligomers, in point mutated alpha-synuclein transgenic mouse. More importantly, we also described the positive effect of PREP inhibition on autophagy – one of the most important cellular mechanisms to remove protein aggregates. This has a high relevance also on other diseases with protein accumulation such as Alzheimer’s and Huntington’s disease, and may well raise the interest on PREP inhibitors as a drug development target.

PhD student Mari Savolainen was the first author of the paper, and this work was done in collaboration with NIDA, Baltimore and Georgetown University, DC. These studies were funded by the Academy of Finland, Jane and Aatos Erkko Foundation, Finnish Parkinson Foundation, Sigrid Juselius Foundation and University of Helsinki grants.

One of the biggest foundations in the field of medicine in Finland, Sigrid Juselius Foundation, decided to continue their support for our studies for 2 more years. This is remarkable grant for our material costs and will certainly strengthen our research. More information about the grants can be found here: http://www.sigridjuselius.fi/apurahat/kotimaiset-apurahat/

Dr. Timo T. Myöhänen was awarded the University of Helsinki three-year research grant for 2014-2016. There was tough competition on the grants – 204 applications and 20 of those were funded. The sum of the grant is alltogether 150 000 €.

Dr. Myöhänen’s group got a remarkable research grant from Jane and Aatos Erkko Foundation. The grant is a continous grant for ongoing grant, and will be 411600 e for 3.5 years. The grant period starts 7/2013 and continues until the end of 2016.

This allows expanding our group and it will certainly strenghten and accelerate our research. To see the list of grants 2013:

http://www.jaes.fi/en/myonnetyt-apurahat/2013-2/

Academy of Finland granted a Research Fellow position for Timo Myöhänen today, 15.5.2013. The position is for 5 years, from September 1st 2013 to August 31st 2018. The grant is remarkable to continue the studies. The abstract (in Finnish) can be found here.

PREP in neurodegenerative diseases -group got another publication on Neuroscience when Mirva Hannula’s manuscript “Prolyl oligopeptidase colocalizes with alpha-synuclein, beta-amyloid, tau protein and astroglia in the post-mortem brain samples with Parkinson’s and Alzheimer’s diseases” got accepted.

In this manuscript, we observed that PREP actually colocalizes with several hallmark proteins of neurodegenerative diseases, such as alpha-synuclein in Parkinson’s and beta-amyloid in Alzheimer’s. This further stresses the role of PREP in neurodegenerative diseases with protein modifications, and opens novel possibilities for further studies.

The manuscript abstract should be available soon online here.

Our PREP group got a 12-month “homing” grant from Sigrid Juselius Foundation. This grant is remarkable to cover material costs of our research.

Sigrid Juselius Foundation is the biggest private foundation supporting solely medical research in Finland. The list of grants can be found here.

Probably the last publication for the year 2012 was accepted to Neuroscience journal. The study “Comparison of motor performance, brain biochemistry and histology of two A30P α-synuclein transgenic mouse strains” was made in collaboration with Professor Pekka Mannisto’s group. The manuscript was also the first PhD thesis publication for Mari Savolainen.

In this study, we compared the behavior and brain biochemistry of two different transgenic animals carrying human alpha-synuclein mutations. The abstract is available at the journal’s website (click here).