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- W2178806395 abstract "OBJECTIVE: To explore the effect of Bexarotene (Bxt) in a murine model of amyotrophic lateral sclerosis (ALS).BACKGROUND: ALS is characterized by progressive damage of motor neurons (MNs) without a curative treatment. There is experimental evidence suggesting that retinoids may be involved in ALS pathogenesis. Bexarotene (Bxt) is a retinoid-X receptor (RXR) agonist used in treatment of cutaneous tumours with a good safety profile. Bxt has been recently suggested to have a beneficial effect in some experimental models of neurodegenerative diseases.DESIGN AND METHODS: Transgenic SOD1 G93A mice were treated with Bxt or vehicle 5 times per week (100 mg/kg) from day 60 onwards.Survival and neuromuscular function, as well as histological and biochemical features were analyzed in both groups.RESULTS: Bxt significantly delayed motor function deterioration, ameliorated the loss of body weight (p< 0.01), and extended mice survival up to 30[percnt] (p< 0.03) of the symptomatic period. Histological analyses of the lumbosacral spinal cord revealed that Bxt markedly delayed the early motor-neuron degeneration occurring at presymptomatic and early symptomatic stages in ALS-transgenic mice (at day 95, MN numbers were 48[percnt] and 72[percnt] of wild type control in vehicle and Bxt-treated mice, respectively; p<0.001). Immunofluorescence techniques demonstrated that Bxt activated the nuclear RXR pathway. Bxt contributed to modulate motor neuron proteostasis, and particularly to reduce both neuronal loss and chromatolytic response. Bxt also induced nucleolar hypertrophy, an index of transcriptional activity, decreased the formation of ubiquitylated inclusions, and modulated lysosomal response. Bxt also contributed to protect the motor neuron environment by reducing reactive astrogliosis.CONCLUSIONS: The neuroprotective effects demonstrated in this model suggest that Bxt could be useful in human neurodegenerative diseases, especially in those involving motor neurons.Supported by : Direccion General de Investigacion of Spain (BFU2011-23983) and Centro de Investigacion en Red sobre Enfermedades Neurodegenerativas (CIBERNED; CB06/05/0037) Disclosure: Dr. Riancho has nothing to disclose. Dr. Ruiz-Soto has nothing to disclose. Dr. Berciano has nothing to disclose. Dr. Berciano has nothing to disclose. Dr. Lafarga has nothing to disclose." @default.
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- W2178806395 date "2015-04-06" @default.
- W2178806395 modified "2023-10-01" @default.
- W2178806395 title "Neuroprotective Effect of Bexarotene in the SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis (P6.104)" @default.
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