Reduction of neuroinflammation by selective inhibition of the N-type calcium channel is beneficial in various animal models of neurodegeneration Dieter Willbold1,2 and Janine Kutzsche2 1Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany; 2Institute of Complex Systems, ICS-6: Structural Biochemistry, Forschungszentrum Jülich, Jülich, Germany
Neuroinflammation is a pathological hallmark of several neurodegenerative diseases. We speculated that reduction of calcium ion influx specifically in neurons should reduce inflammatory cellular signaling. We have identified compounds that specifically inhibited the N-type calcium channel CaV2.2 (NCC) in nanomolar concentrations without affecting the L-type calcium channel. We tested efficacy of one of the compounds in vivo in a spinal nerve ligation (SNL) rat model and a sciatic inflammatory neuritis (SIN) rat model. The observed acute and therapeutic reversion of tactile allodynia shows that the compound hits the NCC also in vivo. The same compound and a second NCC inhibiting compound were tested also in different neurodegenerative animal models. There, we found very significant deceleration of neurodegeneration as shown for example in the SHIRPA assay. Thus, we suggest that reduction of neuroinflammation by specific inhibition of the NCC leads to disease-modifying beneficial effects in animal models.
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