Unveiling the effect of curcumin on ion channels of SBMA motoneuron-derived cells and human IPSC-derived neurons: initial electrophysiological findings.

Abstract

Curcumin (CUR), a bioactive compound extracted from the turmeric (Curcuma longa), has gathered considerable attention in recent years due to its claimed health benefits, including anti-inflammatory, antioxidant, and neuroprotective properties. The dysregulation of ion channel activity and the altered neuronal excitability in neurons has been identified as a key factor in the pathophysiology of neurological disease and a putative pharmacological target for therapeutic options. Therefore, we investigated by whole-cell patch-clamp the CUR's impact on the ionic currents in motoneuron-derived (MN-1) cells modeling SBMA and in human neuro-progenitor-cell (hNPCs)-derived neurons. CUR decreased viability in non-pathological MN-1 cells but showed increased resistance in pathological MN-1 cells, while mature neurons derived from hiPSCs remained unaffected under the same conditions. Electrophysiological studies revealed that CUR inhibits outward and inward currents in both MN-1 cell types, with a more pronounced effect in pathological cells. In hNPC-derived neurons, CUR also inhibited both currents and induced a negative shift in the voltage dependence of activation, suggesting reduced excitability. Our results indicate that further investigations are needed to confirm the role of CUR in the context of neurotherapeutics based on ion channel-targeting pharmacology.