The aim of my research is to find novel drug therapies for neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, that don’t currently have curative treatment. Our long-term research topic has been PREP enzyme and targeting on it with small-molecular compounds, and we have shown that by targeting PREP we can block several toxic features in models of neurodegenerative diseases. Moreover, based on our PREP research we have found similar multitargeting drug targets, and are currently opening novel research lines.
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18 items-
A prolyl oligopeptidase inhibitor reduces tau pathology in cellular models and in mice with tauopathy
Eteläinen, Tony S; Silva, M Catarina; Uhari-Väänänen, Johanna K; De Lorenzo, Francesca; Jäntti, Maria H; Cui, Hengjing; Chavero-Pieres, Marta; Kilpeläinen, Tommi; Mechtler, Christina; Svarcbahs, Reinis; Seppälä, Erin; Savinainen, Juha R; Puris, Elena; Fricker, Gert; Gynther, Mikko; Julku, Ulrika H; Huttunen, Henri J; Haggarty, Stephen J; Myöhänen, Timo T. 2023. Science translational medicine. 15: 1-17 -
Nigrostriatal 6-hydroxydopamine lesions increase alpha-synuclein levels and permeability in rat colon
Cui, Hengjing; Elford, Joshua D; Alitalo, Okko; Perez-Pardo, Paula; Tampio, Janne; Huttunen, Kristiina M; Kraneveld, Aletta; Forsberg, Markus M; Myöhänen, Timo T; Jalkanen, Aaro J. 2023. Neurobiology of aging. 129: 62-71 -
Nonpeptidic Oxazole-Based Prolyl Oligopeptidase Ligands with Disease-Modifying Effects on α-Synuclein Mouse Models of Parkinson's Disease
Kilpeläinen, Tommi P; Pätsi, Henri T; Svarcbahs, Reinis; Julku, Ulrika H; Eteläinen, Tony S; Cui, Hengjing; Auno, Samuli; Sipari, Nina; Norrbacka, Susanna; Leino, Teppo O; Jäntti, Maria; Myöhänen, Timo T; Wallén, Erik AA. 2023. Journal of medicinal chemistry. 66: 7475-7496 -
Removal of proteinase K resistant αSyn species does not correlate with cell survival in a virus vector-based Parkinson's disease mouse model
Eteläinen, Tony S; Kilpeläinen, Tommi P; Ignatius, Adele; Auno, Samuli; De Lorenzo, Francesca; Uhari-Väänänen, Johanna K; Julku, Ulrika H; Myöhänen, Timo T. 2022. Neuropharmacology. 218: -
2-Imidazole as a Substitute for the Electrophilic Group Gives Highly Potent Prolyl Oligopeptidase Inhibitors
Pätsi, Henri T.; Kilpeläinen, Tommi P.; Auno, Samuli; Dillemuth, Pyry M. J.; Arja, Khaled; Lahtela-Kakkonen, Maija K.; Myöhänen, Timo T.; Wallén, Erik A. A.. 2021. Acs medicinal chemistry letters. 12: 1578-1584 -
Deletion or inhibition of prolyl oligopeptidase blocks lithium-induced phosphorylation of GSK3b and Akt by activation of protein phosphatase 2A
Myöhänen, Timo T; Mertens, Freke; Norrbacka, Susanna; Cui, Hengjing. 2021. Basic and clinical pharmacology and toxicology. 129: 287-296 -
Inhibition of prolyl oligopeptidase: A promising pathway to prevent the progression of age-related macular degeneration
Hellinen, Laura; Koskela, Ali; Vattulainen, Elina; Liukkonen, Mikko; Wegler, Christine; Treyer, Andrea; Handin, Niklas; Svensson, Richard; Myöhänen, Timo; Poso, Antti; Kaarniranta, Kai; Artursson, Per; Urtti, Arto. 2021. Biomedicine and pharmacotherapy. 2022; 146: 112501 -
Prolyl oligopeptidase acts as a link between chaperone-mediated autophagy and macroautophagy
Cui, H.; Norrbacka, S.; Myöhänen, T.T.. 2021. Biochemical pharmacology. 2022; 197: 114899 -
Prolyl oligopeptidase inhibition reduces alpha-synuclein aggregation in a cellular model of multiple system atrophy
Cui, Hengjing; Kilpeläinen, Tommi; Zouzoula, Lydia; Auno, Samuli; Trontti, Kalevi; Kurvonen, Sampo; Norrbacka, Susanna; Hovatta, Iiris; Jensen, Poul Henning; Myöhänen, Timo T.. 2021. Journal of cellular and molecular medicine. 25: 9634-9646 -
Prolyl oligopeptidase inhibition reduces oxidative stress via reducing NADPH oxidase activity by activating protein phosphatase 2A
Eteläinen, T; Kulmala, V; Svarcbahs, R; Jäntti, M; Myohänen, T T. 2021. Free radical biology and medicine. 169: 14-23