In-vitro screening for drug-induced neuropathy
2022
University of Konstanz, Konstanz, Germany
In this study, the suitability of matured peripheral neuron cultures for the detection of sub-cytotoxic endpoints, such as altered responses of pain-related P2X receptors is explored. Therefore, human sensory neurons were established from induced pluripotent stem cells and used to assess proteasome inhibitor-induced early alterations in signalling and morphology. Purinergic signalling was exploited as a sensitive endpoint affected by proteasome inhibitors. Moreover, the microtubule arrangement was studied as an indicator of initial morphological stress responses. A panel of five proteasome inhibitors was used to identify readouts of cell changes occurring well before signs of general cytotoxicity. P2X3 signalling proved useful as an endpoint to assess potential neurotoxicants. The presented model may be used for the profiling of new proteasome inhibitors in regard to their side effects (neuropathy) potential, or for pharmacological studies on the attenuation of their neurotoxicity.
Specific attenuation of purinergic signaling during bortezomib-induced peripheral neuropathy in vitro
Marcel Leist
Added on: 05-31-2022
[1] https://www.mdpi.com/1422-0067/23/7/3734
