Tracking down the security guards of the cell: New therapeutic approach for the treatment of cardiovascular diseases
PD Dr. Enno Klußmann
Forschungsverbund Berlin e. V.
Recipient: Forschungsverbund Berlin e. V.
Funding: GO-Bio Phase I (01.01.2008 - 31.05.2009, 1.025.529 Euro)
Recipient: Forschungsverbund Berlin e.V.
Funding: GO-Bio Phase I (01.06.2009 bis 31.10.2011, 1.626.501 Euro)
Despite significant global medical efforts, cardiovascular diseases still count among the most frequent causes of death. Many therapeutic approaches are aimed at influencing the activity of functional proteins, and commonly take the enzymes, ion channels or receptors of a cell as their starting points. However, these proteins frequently assume a range of functions as well as interact with numerous other proteins. For this reason, modified activity can affect both the desired function as well as all other functions, potentially resulting in severe side effects.
In his project, Enno Klußmann is focusing not on the activities but on the interactions with specific partners, including the protein kinase PKA, of the AKAP class of protein. AKAPs (protein kinase A anchor proteins) are special scaffold proteins whose function in the cell is not unlike that of a security guard. These attack the components of cellular signal chains such as PKA, and in this way ensure that a signal will only be processed in specific regions within the cell. It has already been demonstrated that AKAP-dependent interactions with other proteins, in particular with PKA, are involved in the regulation of cardiac muscle cell contraction, as well as in water reabsorption in the principal cells of the kidney. Both cell types are viewed as pivotal in the progression of cardiac insufficiency.
The use of small chemical molecules in the selective suppression of anchor protein interaction with PKA and other partners is at the centre of therapeutic approach for the treatment of cardiac insufficiency that is currently being developed by Klußmann. It is hoped to bring the approach to market maturity in a yet-to-be-founded company. The researcher is pursuing two strategies: In cardiac muscle cells as well as in the principal cells of the kidney, AKAP-dependent protein-protein interactions will be investigated and inhibited as attack points for novel therapeutic agents.