title: Retinoids and motor neuron disease: Potential role in amyotrophic lateral sclerosis.
abstract: Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons (MN). This fatal disease is characterized by progressive muscular atrophy and unfortunately it does not have an effective treatment. Although a small proportion of ALS cases have a familiar origin, the vast majority of them are thought to have a sporadic origin. Although the pathogenesis of ALS has not been fully elucidated, various disorders in different cellular functions such as gene expression, protein metabolism, axonal transport and glial cell disorders have been linked to MN degeneration. Among them, proteostasis is one of the best studied. Retinoids are vitamin A-derived substances that play a crucial role in embryogenesis, development, programmed cell death and other cellular functions. Retinoid agonists behave as transcription factors throughout the activation of the nuclear retinoid receptors. Several reports in the literature suggest that retinoids are involved in proteostasis regulation, by modulating its two major pathways, the ubiquitin-proteasome system and the autophagy-lysosome response. Additionally, there are some evidences for a role of retinoids themselves, in ALS pathogenesis. In this review, we discuss the importance of proteostasis disruption as a trigger for MN degeneration and the capability of retinoids to modulate it, as well as the potential therapeutic role of retinoids as a new therapy in ALS.
authors.affiliation: Service of Neurology, University Hospital Marques de Valdecilla (IDIVAL), CIBERNED, Santander, Spain. Electronic address: javier.riancho86@gmail.com.
authors.forename: Javier
authors.initials: J
authors.lastname: Riancho
authors.affiliation: Anatomy and Cell Biology Department, University of Cantabria-IDIVAL, CIBERNED, Santander, Spain.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Berciano
authors.affiliation: Anatomy and Cell Biology Department, University of Cantabria-IDIVAL, CIBERNED, Santander, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Ruiz-Soto
authors.affiliation: Service of Neurology, University Hospital Marques de Valdecilla (IDIVAL), CIBERNED, Santander, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Berciano
authors.affiliation: Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Landreth
authors.affiliation: Anatomy and Cell Biology Department, University of Cantabria-IDIVAL, CIBERNED, Santander, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Lafarga
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D012176:Retinoids / Q000378:metabolism*
chemical_list: D012176:Retinoids
keywords: Amyotrophic lateral sclerosis; Bexarotene; Neurodegeneration; Retinoids; SOD1