The role of the ubiquitin proteasome system in the memory process.

Quite intuitive is the notion that memory formation and consolidation is orchestrated by protein synthesis because of the synaptic plasticity necessary for those processes. Nevertheless, recent advances have begun accumulating evidences of a high requirement for protein degradation on the molecular mechanisms of the memory process in the mammalian brain. Because degradation determines protein half-life, degradation has been increasingly recognized as an important intracellular regulatory mechanism. The proteasome is the main player in the degradation of intracellular proteins. Proteasomal substrates are mainly degraded after a post-translational modification by a poly-ubiquitin chain. Latter process, namely poly-ubiquitination, is highly regulated at the step of the ubiquitin molecule transferring to the protein substrate mediated by a set of proteins whose genes represent almost 2% of the human genome. Understanding the role of polyubiquitin-mediated protein degradation has challenging researchers in many fields of investigation as a new source of targets for therapeutic intervention, e.g. E3 ligases that transfer ubiquitin moieties to the substrate. The goal of present work was to uncover mechanisms underlying memory processes regarding the role of the ubiquitin-proteasome system (UPS). For that purpose, preceded of a short review on UPS and memory processes a top-down systems biology approach was applied to establish central proteins involved in memory formation and consolidation highlighting their cross-talking with the UPS. According to that approach, the pattern of expression of several elements of the UPS were found overexpressed in regions of the brain involved in processing cortical inputs.

Patent foramen ovale and migraine attacks: a systematic review.

BACKGROUND: Migraine headache and the presence of a patent foramen ovale have been associated with each other, although the precise pathophysiological mechanism(s) are uncertain. The purpose of this systematic review was to identify the extent of patent foramen ovale prevalence in migraineurs and to determine whether closure of a patent foramen ovale would improve migraine headache. METHODS: An electronic literature search was performed to select studies between January 1980 and February 2013 that were relevant to the prevalence of patent foramen ovale and migraine, and the effects of intervention(s) on migraine attacks. Of the initial 368 articles presented by the initial search, 20 satisfied the inclusion criteria assessing patent foramen ovale prevalence in migraineurs and 21 presented data on patent foramen ovale closure. RESULTS: In case series and cohort studies, patent foramen ovale prevalence in migraineurs ranged from 14.6% to 66.5%. Case-control studies reported a prevalence ranging from 16.0% to 25.7% in controls, compared with 26.8% to 96.0% for migraine with aura. The extent of improvement or resolution of migraine headache attack symptoms was variable. In case series, intervention ameliorated migraine headache attack in 13.6% to 92.3% of cases. One single randomized trial did not show any benefit from patent foramen ovale closure. The data overall do not exclude the possibility of a placebo effect for resolving migraine following patent foramen ovale closure. CONCLUSION: This systematic review demonstrates firstly that migraine headache attack is associated with a higher prevalence of patent foramen ovale than among the general population. Observational data suggest that some improvement of migraine would be observed if the patent foramen ovale were to be closed. A proper assessment of any interventions for patent foramen ovale closure would require further large randomized trials to be conducted given uncertainties from existing trial data.

The role of the ubiquitin proteasome system in the memory process

Quite intuitive is the notion that memory formation and consolidation is orchestrated by protein synthesis because of the synaptic plasticity necessary for those processes. Nevertheless, recent advances have begun accumulating evidences of a high requirement for protein degradation on the molecular mechanisms of the memory process in the mammalian brain. Because degradation determines protein half-life, degradation has been increasingly recognized as an important intracellular regulatory mechanism. The proteasome is the main player in the degradation of intracellular proteins. Proteasomal substrates are mainly degraded after a post-translational modification by a poly-ubiquitin chain. Latter process, namely poly-ubiquitination, is highly regulated at the step of the ubiquitin molecule transferring to the protein substrate mediated by a set of proteins whose genes represent almost 2% of the human genome. Understanding the role of polyubiquitin-mediated protein degradation has challenging researchers in many fields of investigation as a new source of targets for therapeutic intervention, e.g. E3 ligases that transfer ubiquitin moieties to the substrate. The goal of present work was to uncover mechanisms underlying memory processes regarding the role of the ubiquitin-proteasome system (UPS). For that purpose, preceded of a short review on UPS and memory processes a top-down systems biology approach was applied to establish central proteins involved in memory formation and consolidation highlighting their cross-talking with the UPS. According to that approach, the pattern of expression of several elements of the UPS were found overexpressed in regions of the brain involved in processing cortical inputs.