We are currently studying also many other transporters and protein targets and there results haven’t published yet. Herein, we list all the ongoing projects and the partners.
Multifunctional metformin derivatives
We have collaborated with Dr. Magdalena Markowicz-Piasecka, from Lodz Medical University, Poland since 2016. Main aim of our collaborative research has been in the development of metformin prodrugs and derivatives that would have greater anti-diabetic and anti-coagulant effects than metformin itself, but we have also studied the novel compounds as anti-cancer agents and as potential acetyl/butyrylcholinesterase inhibitors.
SMVT, CAT1, MCT1, and SNATs
Currently, in addition to LAT1 and OATPs, we are studying also sodium-dependent multivitamin transporter (SMVT, SLC5A6), cationic amino acid transporter 1 (CAT1, SLC7A1), monocarboxylate transporter 1 (MCT1, SLC16A1), as well as the family of sodium-coupled neutral amino acid transporters (SNATs) and their possibilities to be utilized for brain- and intrabrain-targeted delivery, of endogenous compounds (deficiency syndromes) as well as novel drug molecules in their transporter-utilizing prodrug forms. The computational drug design and studying the transport mechanisms of the designed substrates are carried out in a collaborartion with Professor Antti Poso, UEF/Eberhard Karls University of Tübingen (Germany).
Novel agonists to modulate Piezo1 ion channel function
The involvement of Piezo ion channels in mechanosensitive transductions was awarded with a Nobel prize to David Julius and Ardem Patapoutian in 2021. Since 2019, we have collaborated with Professor Tarja Malm (UEF, A.I. Virtanen Institute; Neuroinflammation) to develop novel compounds that could function as a Piezo1 ion channel agonists. Prof. Malm’s group is shown that activation of Piezo1 increases microglial phagocytosis, reduces microglial pro-inflammatory activation, and enhances lysosomal activity, resulting in Aβ clearance both in human and mouse models of Alzheimer’s disease. On the other hand, Piezo1 is also expressed in the lungs and therefore, it is a potential multitarget druggable protein, by which, e.g., COVID-19-induced lung injuries accompanied by neurological complications could be treated.
Protein Phosphatase 2A (PP2A)
In collaboration, with Professor Timo Myöhänen (UEF, School of Pharmacy; Pharmacology) we are currently developing a novel activators of protein phosphatase 2A (PP2A) that could be utilized to treat neurodegenerative diseases with amberrant tau protein, so called tauopathies, such as Alzheimer’s disease, Parkinson’s diseases and Frontotemporal dementia. PP2A is the primary enzyme (phosphatase) to phophorylate or cleave the phosphate groups of hyperphosporylated tau protein, and PP2A dysfunction has been linked to pathological hallmarks of neurodegenerative disorders. Therefore, modulation PP2A function is highly interesting approach to treat several neurodegenerative diaseses. This collaboration, that has been initiated in 2019-2020, involves also molecular modelling of the target protein, carried out by Dr. Maija Lahtela-Kakkonen (UEF, Shool of Pharmacy; Pharmaceutical Chemistry).
Since 2021, we have collaborated with Professor Jaana Rysä (UEF, School of Pharmacy; Toxicology) to figure out changes in placental proteome and metabolome related to diabetes. Therefore, we aim to identify placental proteome and metabolites that could serve as a predictive biomarkers for wellbeing of the fetus and post-natal development as well as putative gender-specific molecular mechanisms linking diabetes with adverse outcomes of aberrant of growth of the fetus.