RESUMO
Roquin-1 (Rc3h1) is an E3 ubiquitin ligase originally discovered in a mutational screen for genetic factors contributory to systemic lupus erythematosus-like symptoms in mice. A single base-pair mutation in the Rc3h1 gene resulted in the manifestation of autoantibody production and sustained immunological inflammation characterized by excessive T follicular helper cell activation and formation of germinal centers. Subsequent studies have uncovered a multifactorial process by which Roquin-1 contributes to the maintenance of immune homeostasis. Through its interactions with partner proteins, Roquin-1 targets mRNAs for decay with inducible costimulator being a primary target. In this review, we discuss newly discovered functions of Roquin-1 in the immune system and inflammation, and in disease manifestation, and discuss avenues of further research. A model is presented for the role of Roquin in health and disease.
Assuntos
Autoanticorpos/biossíntese , Homeostase/imunologia , Proteína Coestimuladora de Linfócitos T Induzíveis/genética , Lúpus Eritematoso Sistêmico/genética , Proteínas de Ligação a RNA/genética , Ubiquitina-Proteína Ligases/genética , Animais , Modelos Animais de Doenças , Regulação da Expressão Gênica , Centro Germinativo/imunologia , Centro Germinativo/patologia , Homeostase/genética , Humanos , Imunidade Inata , Proteína Coestimuladora de Linfócitos T Induzíveis/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Ativação Linfocitária , Camundongos , Mutação , Proteínas de Ligação a RNA/imunologia , Receptores do Fator de Necrose Tumoral/genética , Receptores do Fator de Necrose Tumoral/imunologia , Transdução de Sinais , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/patologia , Ubiquitina-Proteína Ligases/imunologiaRESUMO
AIM: The aim of the study was to investigate the sustainability of motor improvements achieved after a three week trial of robotic assisted treadmill therapy in children and adolescents with central gait disorders within a follow up period of about six months. METHODS: Open, non-randomized, baseline-treatment study. Fourteen patients (mean age 8.2+/-5.4) underwent a trial of 12 sessions of robotic-assisted treadmill therapy using the Lokomat over a period of three weeks. Outcome measures were the dimensions D (standing) and E (walking) of the Gross Motor Function Measure, the ten meter walking test and the six minute walking test. Outcome variables were evaluated immediately before and after the trial and at a follow up of about six months. RESULTS: Improvements after the trial in the dimension D from 49.5% to 54.4% (P=0.008) and from 38.9% to 42.3% (P=0.012) in the dimension E of the GMFM were seen and are within the same range of previously published results. The mean score at the follow up after six months was 56.8% and 43.3% for dimension D and E, respectively. Gait speed improved from 0.80 m/s to 1.01 m/s (P=0.006) after the trial and was 1.11 m/s at the follow-up visit at six months. Similar results were obtained for endurance. CONCLUSION: The improvements of motor function after a three-week trial of robotic-assisted treadmill therapy appear to be sustained after a mean period of six months.