An international team with the participation of Cologne has defined a new mechanism for the development of Parkinson's disease, which could prove to be the starting point for the development of targeted therapy for Parkinson's disease. The result was published in the journal Nature Communications under the title "Cav2.3 channels contribute to the loss of dopaminergic neurons in a model of Parkinson's disease".
Parkinson's disease is a neurodegenerative disease that selectively kills a particular group of dopamine-producing neurons in the midbrain. The resulting dopamine deficiency leads to symptoms such as shivering, muscle stiffness and problems with voluntary movements. Parkinson's disease is the second most common neurodegenerative disease affecting more than six million people worldwide. The occurrence of Parkinson's disease is very dependent on age, but in many respects it is poorly understood. Especially because various causes – from genetic disposition around environmental factors to drug use – can contribute to the development of this disease. Causal therapy is currently not possible. Therefore, efforts are underway worldwide to better understand the molecular mechanisms of this disease.
In this context, there has long been clear evidence that, at the cellular level, disorders of calcium-dependent signaling pathways are significantly involved or associated with the development of Parkinson's disease. Calcium is involved in many cellular signaling pathways and its concentration is therefore very precisely regulated in the cell.
Deregulation of calcium balance causes disruption of intracellular signaling cascades, which can lead to cell death. An international team under Cologne's involvement has shown that too strong a strong influx of calcium through specific ion channels, the Cav2.3 channels of the so-called R-type, can significantly contribute to the development of Parkinson's disease. In a Parkinson's model on a mouse model organism, researchers have been able to prevent the death of dopamine-producing neurons by genetically interrupting Cav2.3 channel activity. The Cav2.3 ion channel is not associated with Parkinson's disease. Further studies on dopamine-derived neurons derived from human-induced so-called pluripotent stem cells show that similar signaling cascades also affect human neurons, such as those causing Parkinson's disease susceptibility in an animal model.
Previously, it was suggested that another calcium channel, Cav1.3 (L-type calcium channel), was centrally involved in the development of Parkinson's disease. However, a recent clinical trial blocking Cav1.3 channels showed no protection against Parkinson's disease. A new study provides clues as to why this clinical trial did not show protective effects and suggests testing for selective Cav2.3 inhibitors as a Parkinson's drug.
Prof. Peter Kloppenburg
Biozentrum, Institute of Zoology, University of Cologne, CECAD
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