A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Prolyl oligopeptidase inhibition reduces alpha-synuclein aggregation in a cellular model of multiple system atrophy
Tekijät: Cui Hengjing, Kilpeläinen Tommi, Zouzoula Lydia, Auno Samuli, Trontti Kalevi, Kurvonen Sampo, Norrbacka Susanna, Hovatta Iiris, Jensen Poul Henning, Myöhänen Timo T
Kustantaja: WILEY
Julkaisuvuosi: 2021
Lehti: Journal of Cellular and Molecular Medicine
Tietokannassa oleva lehden nimi: JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Lehden akronyymi: J CELL MOL MED
Vuosikerta: 25
Numero: 20
Aloitussivu: 9634
Lopetussivu: 9646
Sivujen määrä: 13
ISSN: 1582-1838
eISSN: 1582-4934
DOI: https://doi.org/10.1111/jcmm.16910
Verkko-osoite: https://doi.org/10.1111/jcmm.16910
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/67339883
Multiple system atrophy (MSA) is a fatal neurodegenerative disease where the histopathological hallmark is glial cytoplasmic inclusions in oligodendrocytes, rich of aggregated alpha-synuclein (aSyn). Therefore, therapies targeting aSyn aggregation and toxicity have been studied as a possible disease-modifying therapy for MSA. Our earlier studies show that inhibition of prolyl oligopeptidase (PREP) with KYP-2047 reduces aSyn aggregates in several models. Here, we tested the effects of KYP-2047 on a MSA cellular models, using rat OLN-AS7 and human MO3.13 oligodendrocyte cells. As translocation of p25 alpha to cell cytosol has been identified as an inducer of aSyn aggregation in MSA models, the cells were transiently transfected with p25 alpha. Similar to earlier studies, p25 alpha increased aSyn phosphorylation and aggregation, and caused tubulin retraction and impaired autophagy in OLN-AS7 cells. In both cellular models, p25 alpha transfection increased significantly aSyn mRNA levels and also increased the levels of inactive protein phosphatase 2A (PP2A). However, aSyn or p25 alpha did not cause any cellular death in MO3.13 cells, questioning their use as a MSA model. Simultaneous administration of 10 mu M KYP-2047 improved cell viability, decreased insoluble phosphorylated aSyn and normalized autophagy in OLN-AS7 cells but similar impact was not seen in MO3.13 cells.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
