Timo Myöhänen, PhD, Professor of Pharmacology, Helsinki University

The Department of Chemistry Presents: Timo Myöhänen, PhD, Professor of Pharmacology, Helsinki University 

Neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, affect millions of people globally. Current medications are mainly symptomatic and cannot stop or delay the process of neuronal death, leading to more severe symptoms. Novel beta-amyloid antibodies for Alzheimer’s disease then again have minor disease-modifying effect but they have serious adverse effects and are not suitable for most of the patients. Therefore, novel therapeutic targets are needed to develop effective disease-modifying therapy.

 

There are several pathophysiological mechanisms in neurodegenerative diseases that eventually lead to neuronal death, such as protein accumulation, neuroinflammation and oxidative stress. One reason for poor success in drug development might be that usually drug candidates for neurodegenerative disease target on one pathophysiological mechanism. A key for effective disease-modifying therapy could be a to find a target that has effect on various pathophysiological mechanisms. One such target is protein phosphatase 2A (PP2A), a major phosphate in cell that has impact on protein stability and processing, inflammation and several other processes related to neurodegenerative diseases. Additionally, PP2A activity has been shown to be decreased in various neurodegenerative diseases. However, PP2A is also difficult drug target, and so far, no PP2A activating therapies have been developed for clinical use.

 

The  Myöhänen Lab's approach to activate PP2A is to develop small-molecular ligands to interfere a ubiquitin ligase, MID1, for transporting PP2A to proteasomal degradation. We have synthesized novel MID1 targeting ligands and shown that they can elevate PP2A levels in cell cultures and primary neurons. Moreover, they have shown beneficial effects on protein aggregation and neuroinflammation in the Alzheimer’s disease models.

 

The  Myöhänen Lab's ambitious aim is to find a way to stop neurodegenerative diseases, such as Alzheimer's and Parkinson's disease, where there are not yet effective disease-modifying therapies available. NeuroCure lab focuses on the potential major causes for neuronal death, protein aggregation, protein processing failures, oxidative stress and neuroinflammation that are common for features in several neurodegenerative diseases. Their long term focus has been prolyl oligopeptidase (PREP, POP) and its ligands that have shown disease-modifying effects on various models of neurodegenerative diseases.