Invited Review: Decoding the pathophysiological mechanisms that underlie RNA dysregulation in neurodegenerative disorders: a review of the current state of the art

Altered RNA metabolism is a key pathophysiological component causing several neurodegenerative diseases. Genetic mutations causing neurodegeneration occur in coding and noncoding regions of seemingly unrelated genes whose products do not always contribute to the gene expression process. Several pathogenic mechanisms may coexist within a single neuronal cell, including RNA/protein toxic gain-of-function and/or protein loss-of-function. Genetic mutations that cause neurodegenerative disorders disrupt healthy gene expression at diverse levels, from chromatin remodelling, transcription, splicing, through to axonal transport and repeat-associated non-ATG (RAN) translation. We address neurodegeneration in repeat expansion disorders [Huntington's disease, spinocerebellar ataxias, C9ORF72-related amyotrophic lateral sclerosis (ALS)] and in diseases caused by deletions or point mutations (spinal muscular atrophy, most subtypes of familial ALS). Some neurodegenerative disorders exhibit broad dysregulation of gene expression with the synthesis of hundreds to thousands of abnormal messenger RNA (mRNA) molecules. However, the number and identity of aberrant mRNAs that are translated into proteins – and how these lead to neurodegeneration – remain unknown. The field of RNA biology research faces the challenge of identifying pathophysiological events of dysregulated gene expression. In conclusion, we discuss current research limitations and future directions to improve our characterization of pathological mechanisms that trigger disease onset and progression

Factores protectores frente al consumo de alcohol: concepción de maestros de nivel inicial Fatores protetores frente ao consumo de álcool: percepção de professores de educação básica Protection factors against alcohol consumption as perceived by basic education teachers

Esta investigación busca comprender la concepción de maestros de nivel inicial sobre los factores protectores frente al consumo de alcohol, basándose en los modelos teóricos de Resiliencia y Promoción de la Salud. De enfoque metodológico cualitativo, exploratorio, aplica entrevistas semi-estructuradas y observación no estructurada a una muestra de 25 maestras. Del análisis de contenido de los datos surgen tres categorías temáticas: Significado de Alcohol/Alcoholismo - interpretado como sustancia nociva y situación problema socio-cultural -; La Escuela como Espacio de Protección Frente al Consumo de Alcohol; El Maestro como Agente de Protección. Se asocia protección con informar hasta cuidar. El maestro entiende su función desde orientador hasta consejero/protector, para la cual, mayoritariamente, no se siente preparado fundamentándose en déficits psicopedagógicos, cognocistivos, jurídico-legales y por propios prejuicios sobre alcoholismo. Los resultados confirman los presupuestos de la investigación relativos al maestro y contexto escolar.<br>O objetivo desta pesquisa é entender a percepção de professores de educação básica sobre os fatores que protegem contra o consumo de álcool. Foi adotada uma metodologia qualitativa do tipo exploratório, com entrevistas semi-estruturadas e observação não-estruturada aplicadas a uma amostra de 25 professoras. A análise de conteúdo dos dados levantou três categorias temáticas: Significado de Álcool/Alcoolismo; A Escola como Espaço de Proteção contra o Consumo de Álcool; o Professor como Agente de Proteção. O primeiro é interpretado como uma substância nociva e uma situação problema sócio-cultural. A proteção é associada com informar, comunicar, educar, ou cuidar. Portanto, o professor compreende sua função como cobrindo desde orientador até conselheiro ou protetor. A maioria não se sente preparada para desempenhá-la, fundamentando-se em déficits psicopedagógicos, conhecimentos de saúde integral, o arcabouço jurídico-legal e, principalmente, seus próprios preconceitos sobre alcoolismo.<br>This research aims to understand how basic education teachers perceive factors that protect against alcohol consumption. An exploratory qualitative methodological approach is adopted. Semi-structured interviews and non-structured observation techniques are applied to a sample of 25 teachers. Content analysis of data gave rise to three thematic categories: the Meaning of Alcohol/Alcoholism; The School as an Area of Protection against Alcohol Consumption; the Teacher as a Protective Agent. The first one is interpreted as a harmful substance and a sociocultural problem situation. Protection is linked up with informing, communicating, educating or caring. Thus, the way teachers see their function ranges from guide to adviser or protector. Most teachers do not feel prepared for it, on the basis of psychopedagogical deficits, integral health knowledge, the legal framework and, mainly, their own prejudices on alcoholism