| Autor: |
Sánchez-Sanz A; Neuroimmunology Unit, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, 28222 Madrid, Spain., Coronado-Albi MJ; Confocal Microscopy Core Facility, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, 28222 Madrid, Spain., Muñoz-Viana R; Bioinformatics Unit, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, 28222 Madrid, Spain., García-Merino A; Neuroimmunology Unit, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, 28222 Madrid, Spain.; Department of Neurology, Hospital Universitario Puerta de Hierro Majadahonda, 28222 Madrid, Spain.; Department of Medicine, Universidad Autónoma de Madrid, 28049 Madrid, Spain.; Red Española de Esclerosis Múltiple (REEM), 08028 Barcelona, Spain., Sánchez-López AJ; Neuroimmunology Unit, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, 28222 Madrid, Spain.; Red Española de Esclerosis Múltiple (REEM), 08028 Barcelona, Spain.; Biobank, Instituto de Investigación Sanitaria Puerta de Hierro-Segovia de Arana, 28222 Madrid, Spain. |
| Abstrakt: |
Dimethyl fumarate (DMF) is an immunomodulatory treatment for multiple sclerosis (MS) that can cross the blood-brain barrier, presenting neuroprotective potential. Its mechanism of action is not fully understood, and there is a need to characterize whether DMF or its bioactive metabolite monomethyl fumarate (MMF) exerts neuroprotective properties. Moreover, the combination of adjuvant agents such as cannabidiol (CBD) could be relevant to enhance neuroprotection. The aim of this study was to compare the neuroprotective and immunomodulatory effects of DMF, MMF, and CBD in neurons and microglia in vitro. We found that DMF and CBD, but not MMF, activated the Nrf2 antioxidant pathway in neurons. Similarly, only DMF and CBD, but not MMF, prevented the LPS-induced activation of the inflammatory pathway NF-kB in microglia. Additionally, the three drugs inhibited the production of nitric oxide in microglia and protected neurons against apoptosis. Transcriptomically, DMF modulated a greater number of inflammatory and Nrf2-related genes compared to MMF and CBD in both neurons and microglia. Our results show that DMF and MMF, despite being structurally related, present differences in their mechanisms of action that could be relevant for the achievement of neuroprotection in MS patients. Additionally, CBD shows potential as a neuroprotective agent. |
