Regenerative pharmacology

Regenerative Pharmacology group has its focus on novel drug targets and experimental drugs to reveal the basis of disease modifying therapies of illnesses with unmet medical need, especially degenerative heart and - brain diseases (including drug and alcohol addiction). We explore possibilities of tissue repair by inducing proliferation and differentiation of adult stem cells in the heart and in the brain by chemical and/or protein drugs. Dissolution and imaging of aberrant proteins in the brain relevant to Parkinson’s disease as well as levodopa-induced dyskinesias are in focus. Therapeutic drug targets include transcription factors, protein kinase C (PKC), prolyl oligopeptidase and cell surface receptors such as nicotinic and histaminergic receptors and receptors involved in drug addiction. Unit's principal investigators are listed below.

The aim of the research is to find basis for disease modifying drug therapies of neurodegenerative diseases, i.e. Alzheimer’s disease (AD) and Parkinson’s disease (PD). In AD we concentrate on experimental drugs that modify activity of protein kinase C (PKC). Our focus is on PKC partial agonists that would reduce formation of aberrant amyloid beta fragments. In PD we explore possibilities to induce adult neural stems cells in sub ventricular zone and differentiate them to mature neurons in striatum. We also study effects and mechanisms of action of neurotrophic factors in experimental PD. In this respect novel neurotrophic factors CDNF and MANF are promising disease modifying therapies with unique mechanism of action

Imaging. Development of new tracers for neuroinflammation, disease bio-marking; characterisation of models of neurodegenerative disease in rodents for the validation of new therapeutic approaches against the disease. Developing new imaging systems for drug absorption.

Prolyloligopeptidase. Implication of prolyl specific peptidases role as drug targets, studying their biochemistry, molecular biology and cell biology, their physiological relevance on the molecular mechanisms of neuroinflammation, neurodegeneration and clinical cases of multiple sclerosis and hepatic encephalopathy.

Our research is focused on understanding the mechanisms of how prolyl oligopeptidase, PREP, increases the accumulation of aggregation-prone proteins in neurodegenerative diseases, and studying if small-molecule PREP inhibitors are effective in preventing the protein accumulation or even dissolve the surplus of toxic protein aggregates from cells. Currently, a lot of our research efforts are also in studying the role and mechanisms of PREP and its inhibition on autophagic clearance of protein aggregates, and to characterize and develop novel PREP inhibitor molecules.

Doc. Piepponen is an expert in neurochemical analysis. He has set up and maintains the HPLC systems for the analysis of monoamines and amino acid neurotransmitters from large array of matrices, including cerebral tissue samples and microdialysates. These systems are widely used also in cooperation with several other units and industry. Doc. Piepponen is also an expert in ethical issues of experimental animals and statistical testing. His main research interest is the role dopaminergic neurotransmission in drug and alcohol addiction.

The research group studies novel interventions for preventing myocardial remodeling or to activate regenerative pathways. In particular, transcription factors are the main focus as potential targets for new pharmaceuticals. The group also investigates signaling mechanisms involved in myocardial remodeling caused by myocardial infarction and hypertension and the role of natriuretic peptides (ANP and BNP) in heart failure. In addition, a new area of interest is research on the heart regeneration by means of induction of the differentiation of cardiac stem cells into cardiomyocytes, proliferation of cardiomyocytes and direct reprogramming of fibroblasts into cardiomyocytes. Finally, with collaborators the group examines novel drug delivery approaches to target cardioprotective compounds into the border zone of infarcted myocardium.

Outi Salminen leads a research group which is focused on levodopa-induced dyskinesia in Parkinson’s Disease (PD). Levodopa is a cornerstone in PD medication, but its long-term use can lead to severe and bothersome side-effects: dyskinesia, which are abnormal involuntary movements.  Our group is currently broadening its research focus also to the non-motor symptoms of PD. In addition, Outi Salminen group is doing basic research on brain nicotinic and histamine receptors and studying their role in PD and addiction.