RESUMO
Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron disease characterized by degeneration of motor neuron and glial activation followed by the progressive muscle loss and paralysis. Numerous distinct therapeutic interventions have been examined but currently ALS does not have a cure or an efficacious treatment for the disorder. Glutamate- induced excitotoxicity, inflammation, mitochondrial dysfunction, oxidative stress, protein aggregation, transcription deregulation, and epigenetic modifications are associated with the pathogenesis of ALS and known to be therapeutic targets in ALS. In this review, we discuss translational pharmacological studies targeting epigenetic components to ameliorate ALS. Understanding of the epigenetic mechanisms will provide novel insights that will further identify potential biological markers and therapeutic approaches for treating ALS. A combination of treatments that modulate epigenetic components and multiple targets may prove to be the most effective therapy for ALS.
Assuntos
Esclerose Lateral Amiotrófica/patologia , Epigênese Genética , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/terapia , Animais , Inibidores de Histona Desacetilases/uso terapêutico , Histona Desacetilases/química , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Humanos , Ácidos Hidroxâmicos/uso terapêutico , Neurônios Motores/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1 , Ácido Valproico/uso terapêuticoRESUMO
A new one-pot procedure for the efficient synthesis of novel 3-substituted morpholin-2-one-5-carboxamide derivatives using commercially available glycolaldehyde dimer as a bifunctional component with various alpha-amino acids and isocyanides by the Ugi five-center three-component reaction (U-5C-3CR) was developed. [reaction: see text]
RESUMO
Various beta,gamma-unsaturated ketones were successfully prepared by cross-coupling reactions of methyl vinyl ketone (MVK) with benzaldehydes mediated by In/InCl(3) in aqueous media.
RESUMO
We have developed a simple and stereoselective method for synthesizing novel dipeptide isosteres using nitrile oxide cycloaddition as a key reaction. Employing this method, we have prepared efficiently various peptidomimetics containing 2-isoxazolines and alpha-hydroxy ketomethylene dipeptide isosteres.
