RESUMO
Despite being clinically described 150 years ago, the mechanisms underlying amyotrophic lateral sclerosis (ALS) pathogenesis have not yet been fully understood. Studies in both animal models of ALS and human patients reveal a plethora of alterations such as increased glutamate-mediated excitotoxicity, redox stress, increased apoptosis, defective axonal transport, protein-misfolding events, mitochondrial impairment and sustained unregulated immune responses. Regardless of being sporadic or familiar ALS, the final outcome at the cellular level is the death of upper and lower motor neurons, and once diagnosed, ALS is typically lethal within the next 5 years. There are neither clear biomarkers nor therapeutic or disease-modifying treatments for ALS.Accumulating evidence supports the concept that epigenetic-driven modifications, including altered chromatin remodelling events, RNA editing and non-coding RNA molecules, might shed light into the pathogenic mechanisms underlying sporadic/familiar ALS onset and/or severity to facilitate the identification of effective therapies, early diagnosis and potentially early-stage therapeutic interventions to increase the survival outcome of ALS patients.
Assuntos
Esclerose Lateral Amiotrófica/genética , Epigênese Genética/genética , Regulação da Expressão Gênica/genética , Acetilação , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/patologia , Animais , Metilação de DNA/genética , Modelos Animais de Doenças , Exposição Ambiental , Interação Gene-Ambiente , Código das Histonas/genética , Inibidores de Histona Desacetilases/uso terapêutico , Histona Desacetilases/fisiologia , Humanos , MicroRNAs/genética , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Mutação , Estresse Oxidativo , Processamento de Proteína Pós-Traducional , Riluzol/uso terapêutico , Superóxido Dismutase-1/deficiência , Superóxido Dismutase-1/genéticaRESUMO
The effect of in vivo exposure of mice to a 60 Hz sinusoidal magnetic field (MF) at 2.0 mT on male germ cells was studied. The cytological endpoints measured included meiotic chromosome aberrations in spermatocytes and sperm morphology. Three independent experiments were carried out: (a) animals exposed for 72 h, (b) 10 days/8 h daily, and (c) 72 h exposure to MF plus 5 mg/kg of Mitomycin-C. No statistically significant differences indicative of MF effects were observed between MF exposed and control animals. In addition, an opposite effect between MF exposure and Mitomycin-C treatment in terms of chromosomal aberrations and sperm morphology was observed.
