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SFB-F44 - Cell signaling in chronic CNS disorders

Project 02:
Role of L-type Ca2+ channels for Parkinson's Disease and their role for neuroprotection

Jörg Striessnig and Alexandra Koschak

In this project we investigate the individual roles of different L-type Ca2+ channel isoforms for the pathophysiology of Parkinson's Disease and L-DOPA induced dyskineasias. These aspects are or immediate relevance for the future development of novel  L-type Ca2+ channel blockers as novel therapeutics for this disease. Ca2+ channels are important for the physiological function of dopamine neurons in the substantia nigra but the intracellular Ca2+ signals they induce may also contribute to the special vulnerability of these neurons to cell death as observed  in Parkinson's Disease brains. The contribution of different Ca2+ channel isofomes for this process will be evaluated as well as the role of their functionally diverse splice variants. Since these channels also appear to have a role in the side effects caused after long-term L-DOPA therapy, their individual roles in this process will also be studied. This work provides the molecular basis for the future developmnt of isoform-specific  channel blockers.