1. Development of a novel in vitro assay to screen for neuroprotective drugs against iatrogenic neurite shortening
- Author
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Javier Burgueño, Manuel Merlos, María Isabel Loza, Antón L. Martínez, Mateo Barro, Xavier Monroy, and José Brea
- Subjects
Iatrogenic Disease ,Pregabalin ,Drug Evaluation, Preclinical ,Pharmacology ,Biochemistry ,Nitrendipine ,Animal Cells ,Ganglia, Spinal ,Medicine and Health Sciences ,Melatonin ,Neurons ,Analgesics ,Multidisciplinary ,Voltage-dependent calcium channel ,Thioctic Acid ,Antimicrobials ,Pharmaceutics ,Drugs ,Cell Differentiation ,Antivirals ,Neuroprotective Agents ,Vincristine ,Neuropathic pain ,Medicine ,Cellular Types ,medicine.drug ,Research Article ,Neurite ,medicine.drug_class ,Science ,Pain ,Neuroprotection ,Microbiology ,Cell Line ,Signs and Symptoms ,Drug Therapy ,Microbial Control ,Virology ,medicine ,Neurites ,Humans ,Neuropathic Pain ,business.industry ,Rilpivirine ,Biology and Life Sciences ,Cell Biology ,Neuronal Dendrites ,Hormones ,Felodipine ,Cellular Neuroscience ,Neuralgia ,Antiviral drug ,Clinical Medicine ,business ,Neuroprotectives ,Neuroscience ,Developmental Biology - Abstract
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 MT1receptor, 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.
- Published
- 2021