Triplet repeat RNA structure and its role as pathogenic agent and therapeutic target

This review presents detailed information about the structure of triplet repeat RNA and addresses the simple sequence repeats of normal and expanded lengths in the context of the physiological and pathogenic roles played in human cells. First, we discuss the occurrence and frequency of various trinucleotide repeats in transcripts and classify them according to the propensity to form RNA structures of different architectures and stabilities. We show that repeats capable of forming hairpin structures are overrepresented in exons, which implies that they may have important functions. We further describe long triplet repeat RNA as a pathogenic agent by presenting human neurological diseases caused by triplet repeat expansions in which mutant RNA gains a toxic function. Prominent examples of these diseases include myotonic dystrophy type 1 and fragile X-associated tremor ataxia syndrome, which are triggered by mutant CUG and CGG repeats, respectively. In addition, we discuss RNA-mediated pathogenesis in polyglutamine disorders such as Huntington's disease and spinocerebellar ataxia type 3, in which expanded CAG repeats may act as an auxiliary toxic agent. Finally, triplet repeat RNA is presented as a therapeutic target. We describe various concepts and approaches aimed at the selective inhibition of mutant transcript activity in experimental therapies developed for repeat-associated diseases

Tracking the implicit self using event-related potentials

Negative biases in implicit self-evaluation are thought to be detrimental to subjective well-being and have been linked to various psychological disorders, including depression. An understanding of the neural processes underlying implicit self-evaluation in healthy subjects could provide a basis for the investigation of negative biases in depressed patients, the development of differential psychotherapeutic interventions, and the estimation of relapse risk in remitted patients. We thus studied the brain processes linked to implicit self-evaluation in 25 healthy subjects using event-related potential (ERP) recording during a self-relevant Implicit Association Test (sIAT). Consistent with a positive implicit self-evaluation in healthy subjects, they responded significantly faster to the congruent (self-positive mapping) than to the incongruent sIAT condition (self-negative mapping). Our main finding was a topographical ERP difference in a time window between 600 and 700 ms, whereas no significant differences between congruent and incongruent conditions were observed in earlier time windows. This suggests that biases in implicit self-evaluation are reflected only indirectly, in the additional recruitment of control processes needed to override the positive implicit self-evaluation of healthy subjects in the incongruent sIAT condition. Brain activations linked to these control processes can thus serve as an indirect measure for estimating biases in implicit self-evaluation. The sIAT paradigm, combined with ERP, could therefore permit the tracking of the neural processes underlying implicit self-evaluation in depressed patients during psychotherapy