RT Journal Article
T1 Development of a novel in vitro assay to screen for neuroprotective drugs against iatrogenic neurite shortening
A1 Martínez Rodríguez, Antón Leandro
A1 Brea Floriani, José Manuel
A1 Barro Fernández, Mateo
A1 Monroy, Xavier
A1 Merlos, Manuel
A1 Burgueño Hurtado, Javier
A1 Loza García, María Isabel
AB This work tries to help overcome the lack of relevant translational screening assays, as a limitation for the identification of novel analgesics for neuropathic pain. Hyperexcitability and neurite shortening are common adverse effects of antiviral and antitumor drugs, leading to neuropathic pain. Now, as seen in the drug screening that we developed here, a high-content microscopy-based assay with immortalized dorsal root ganglia (DRG) neurons (differentiated F11 cells) allowed to identify drugs able to protect against the iatrogenic neurite shortening induced by the antitumor drug vincristine and the antiviral drug rilpivirine. We observed that vincristine and rilpivirine induced a significant reduction in the neurite length, which was reverted by α-lipoic acid. We had also evidenced protective effects of pregabalin and melatonin, acting through the α2δ-2 subunit of the voltage-dependent calcium channels and the MT1 receptor, respectively. Additionally, two hits originated from a previous primary screening aimed to detect inhibitors of hyperexcitability to inflammatory mediators in DRG neurons (nitrendipine and felodipine) also prevented neurite shortening in our model. In summary, in this work we developed a novel secondary assay for identifying hits with neuroprotective effect against iatrogenic neurite shortening, consistent with the anti-hyperexcitability action previously tested: highlighting nitrendipine and felodipine against iatrogenic damage in DRG neurons.
PB Public Library of Science
YR 2021
FD 2021-03-10
LK https://hdl.handle.net/10347/45391
UL https://hdl.handle.net/10347/45391
LA eng
NO Martínez, A. L., Brea, J., Barro, M., Monroy, X., Merlos, M., Burgueño, J., & Loza, M. I. (2021). Development of a novel in vitro assay to screen for neuroprotective drugs against iatrogenic neurite shortening. PloS one, 16(3), e0248139. https://doi.org/10.1371/journal.pone.0248139
NO This work was supported by the Joint R&D Unit Esteve-USC (IN853A-2017/6), co-funded by the Galician Innovation Agency and the Spanish Ministry of Economy and Competitiveness (MINECO) within the framework of the Spanish Strategy of Innovation in Galicia; by the Phenopain project (RTC-2015-4207-1) of the RETOS-COLABORACIÓN program of the MINECO. This work was also co-funded by the European Union through the European Regional Development Fund (ERDF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. WeLab Barcelona provided support in the form of salaries for XM, MM and JAB, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.
DS Minerva
RD 24 abr 2026