Efecto del Bexaroteno en ratones transgénicos con esclerosis lateral amiotrófica (ELA)studio histológico y molecular

Zusammenfassung

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease without effective treatment. Some authors suggest that retinoids could be implicated on its pathogenesis. In this study we asses if treatment with bexarotene (Bxt), a retinoid X receptor (RXR) agonist, has a beneficial effect in the murine SOD1G93A model of ALS. Treatment with Bxt, trough an enhanced RXR nuclear expression, increased survival and preserved neuromuscular function, ameliorating motor neuron (MN) loss. This drug seems to exert these effects by modulating cellular proteostasis and decreasing astrogliosis. Complementary histological studies in the transgenic mice showed a neuroprotective response in MNs to the stress of the endoplasmic reticulum, mainly based on: i) stress granules formation; ii) establishment of a perinuclear domain of protein synthesis machinery; and iii) preservation of the nucleolar transcription for ribosome biogenesis. This combined response would try to preserve, at least temporarily, the synthesis of those proteins needed for cell survival.