The disruption of proteostasis in neurodegenerative diseases

Cells count on surveillance systems to monitor and protect the cellular proteome which, besides being highly heterogeneous, is constantly being challenged by intrinsic and environmental factors. In this context, the proteostasis network (PN) is essential to achieve a stable and functional proteome. Disruption of the PN is associated with aging and can lead to and/or potentiate the occurrence of many neurodegenerative diseases (ND). This not only emphasizes the importance of the PN in health span and aging but also how its modulation can be a potential target for intervention and treatment of human diseases.info:eu-repo/semantics/publishedVersio

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

The nascent polypeptide-associated complex is a key regulator of proteostasis

The adaptation of protein synthesis to environmental and physiological challenges is essential for cell viability. Here, we show that translation is tightly linked to the protein folding environment of the cell through the functional properties of the ribosome bound chaperone NAC (nascentpolypeptide-associated complex). Under non-stress conditions, NAC associates with ribosomes to promote translation and protein folding. When proteostasis is imbalanced, NAC relocalizes from a ribosome-associated state to protein aggregates in its role as a chaperone. This results in a functional depletion of NAC from the ribosome that diminishestranslational capacity and the flux of nascent proteins. Depletion of NAC from polysomes and re-localisation to protein aggregates is observed during ageing, in response to heat shock and upon expression of the highly aggregation-prone polyglutamine-expansion proteins and Ab-peptide. These results demonstrate that NAC has a central role as a proteostasis sensor to provide the cell with a regulatory feedback mechanism in which translational activity is also controlled by the folding state of the cellular proteome and the cellular response to stress

Response of human jaw muscles to axial stimulation of a molar tooth

The original publication can be found at www.springerlink.comThe reflexes of the main jaw-closer muscles (masseter and anterior temporalis) on both sides of the jaw were investigated using surface electromyography to observe reflex activity following mechanical stimulation of the 1st right upper-molar tooth at various forces under a number of levels of jaw-muscle activity. As with analogous studies performed on the incisor, three distinct reflex events were identified in the EMG before the earliest conscious subject reaction: early excitation, inhibition and late excitation. However, contrary to observations found during studies on the incisor, excitation, not inhibition was the primary reflex response. The application of a local anaesthetic block around the stimulated molar showed that the primary agents in eliciting the observed reflexes were not contained within the periodontium of the stimulated tooth. A diminished representation of periodontal mechanoreceptors around the molar teeth and more elaborate root structures, hence a more solid connection to the jaw and consequently less tooth movement, were deemed the likely reason for the distinction between the reflex responses of the incisal and molar regions. In addition to the reflex studies, the minimum reaction time of a number of subjects was determined to permit the distinction of a reflex event and an event that could be a conscious subject reaction. It was found that the reaction time of the temporalis muscles was significantly shorter than those of the masseter, while no significant difference was found between the left and right sides. Overall, the data showed that the presence or absence of background muscle activity and subject variability were the main causes of changes in the reflex response, provided the level of the stimulus was greater than 3 N. The application of local anaesthetic had no impact on the reflexes evokedRussell S. A. Brinkworth, Courtney Male and Kemal S. Türke