RESUMO
During translation, messenger RNAs (mRNAs) are decoded by ribosomes which can stall for various reasons. These include chemical damage, codon composition, starvation, or translation inhibition. Trailing ribosomes can collide with stalled ribosomes, potentially leading to dysfunctional or toxic proteins. Such aberrant proteins can form aggregates and favor diseases, especially neurodegeneration. To prevent this, both eukaryotes and bacteria have evolved different pathways to remove faulty nascent peptides, mRNAs and defective ribosomes from the collided complex. In eukaryotes, ubiquitin ligases play central roles in triggering downstream responses and several complexes have been characterized that split affected ribosomes and facilitate degradation of the various components. As collided ribosomes signal translation stress to affected cells, in eukaryotes additional stress response pathways are triggered when collisions are sensed. These pathways inhibit translation and modulate cell survival and immune responses. Here, we summarize the current state of knowledge about rescue and stress response pathways triggered by ribosome collisions.
Assuntos
Biossíntese de Proteínas , Ribossomos , Ubiquitinação , Ribossomos/genética , Ribossomos/metabolismo , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/metabolismoRESUMO
PURPOSE: To report the use of tofacitinib in ten patients with scleritis where the traditional immunomodulation was not successful or could not be used. METHOD: A retrospective chart review. RESULT: Tofacitinib was successful in the treatment of scleritis in patients either recalcitrant to or intolerant to conventional therapy in 9 out of 10 cases reported here. Two patients had developed reactivation of herpetic infection after 1 month of starting tofacitinib. The duration from diagnosis of scleritis to the institution of tofacitinib therapy varied from 1 month to 60 months. Duration of follow-up varies from 2 months to 11 months. CONCLUSION: Tofacitinib can be used as an important future option for managing recurrent and recalcitrant cases of scleritis.