The concept of Targeted Protein Degradation (TPD) has been introduced as an attractive alternative to the development of classical inhibitors. TPD can extend the range of proteins that can be pharmacologically targeted beyond the classical targets for small molecule inhibitors, as a binding pocket is required but its occupancy does not need to lead to inhibition. The method is based on either small molecules that simultaneously bind to a protein of interest and to a cellular E3 ligase and bring them in close proximity (molecular glue) or a bi-functional molecule synthesized from the chemical linkage of a target protein-specific small molecule and one that binds to an E3 ligase (Proteolysis Targeting Chimeras (PROTAC)).
View Article and Find Full Text PDFIn terms of infection control, environmental cleaning is critical in nursing homes, including long term care facilities. According to the statement of the Commission of Hospital Hygiene and Infection Prevention (KRINKO) at the Robert Koch Institute Berlin on the requirements for disinfectants in these areas, procedures should be used that have been certified by the Association for Applied Hygiene (VAH) for the necessary spectrum of efficacy (or are listed accordingly in the disinfectant list of the Robert Koch Institute). Since ozone is a powerfully oxidizing gas with high inhalation toxicity, the conditions of ap-plication and the measures for occupational safety - including ensuring that the limit value in indoor air is not exceeded when handling and using the product -, must be declared by the manufacturer and observed by the staff to exclude toxic long-term hazard.
View Article and Find Full Text PDFBackground: The limited regenerative capacity of injured axons hinders functional recovery after nerve injury. Although no drugs are currently available in the clinic to accelerate axon regeneration, recent studies show the potential of vasohibin inhibition by parthenolide, produced in Tanacetum parthenium, to accelerate axon regeneration. However, due to its poor oral bioavailability, parthenolide is limited to parenteral administration.
View Article and Find Full Text PDFExperimental autoimmune neuritis is a common animal model for acute human immune-mediated polyneuropathies. Although already established in 1955, a number of pathophysiological mechanisms remain unknown. In this study, we extensively characterize experimental autoimmune neuritis progression in Lewis rats, including new insights into the integrity of small nerve fibres, neuropathic pain and macrophage activation.
View Article and Find Full Text PDFTreatments accelerating axon regeneration in the nervous system are still clinically unavailable. However, parthenolide promotes adult sensory neurons' axon growth in culture by inhibiting microtubule detyrosination. Here, we show that overexpression of vasohibins increases microtubule detyrosination in growth cones and compromises growth in culture and in vivo.
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