Members of neuropeptide B/W signaling system have been predominantly detected and mapped within the CNS. In the rat, this system includes neuropeptide B (NPB), neuropeptide W (NPW) and their specific receptor NPBWR1. This signaling system has a wide spectrum of functions including a role in modulation of inflammatory pain and neuroendocrine functions. Expression of NPB, NPW and NPBWR1 in separate heart compartments, dorsal root ganglia (DRG) and stellate ganglia was proven by RT-qPCR, Western blot (WB) and immunofluorescence. Presence of mRNA for all tested genes was detected within all heart compartments and ganglia. The presence of proteins preproNPB, preproNPW and NPBWR1 was confirmed in all the chambers of heart by WB. Expression of preproNPW and preproNPB was proven in cardiac ganglionic cells obtained by laser capture microdissection. In immunofluorescence analysis, NPB immunoreactivity was detected in nerve fibers, some nerve cell bodies and smooth muscle within heart and both ganglia. NPW immunoreactivity was present in the nerve cell bodies and nerve fibers of heart ganglia. Weak nonhomogenous staining of cardiomyocytes was present within heart ventricles. NPBWR1 immunoreactivity was detected on cardiomyocytes and some nerve fibers. We confirmed the presence of NPB/W signaling system in heart, DRG and stellate ganglia by proteomic and genomic analyses.

Tolcapone, a clinically approved drug for the treatment of Parkinson’s disease as an adjunct therapy, has recently emerged as a potential modulator of amyloid‐β aggregation and toxicity, which are hallmark features of Alzheimer’s disease and are also involved in ocular neurodegenerative disorders, including glaucoma and age‐related macular degeneration. Despite these noteworthy findings, the molecular basis of the interaction between amyloid‐β and tolcapone remains poorly understood, and the mechanisms by which tolcapone affects metal–amyloid‐β species have yet to be explored. In this work, we investigate the binding interactions of tolcapone with both copper‐free amyloid‐β and copper‐associated amyloid‐β complexes, using a combination of techniques including UV–vis spectroscopy, circular dichroism, mass spectrometry, and surface plasmon resonance. The results reveal that tolcapone binds directly to amyloid‐β monomers. Furthermore, in vitro assays confirm the capacity of tolcapone to act as a radical scavenger and to compete with amyloid‐β for the binding of copper ions. Altogether, our findings suggest that tolcapone exerts a multifaceted protective effect, potentially inhibiting toxic metal‐free and metal aggregation pathways by preventing metal coordination to amyloid‐β or disrupting preformed amyloid‐β–metal complexes, thus offering new perspectives to explore and develop its analogs for the treatment of neurodegenerative disorders.

Background: The neuropeptide B/W signalling system (NPB/W) has been identified in multiple body regions and is integral to several physiological processes, including the regulation of food intake and energy homeostasis. Recently, it has also been detected in human skin; however, its specific functions in this context remain to be thoroughly investigated. This study aims to identify the expression of neuropeptides B/W receptor 1 (NPBWR1) and neuropeptides B/W receptor 2 (NPBWR2) in human dermal fibroblasts of mesenchymal origin using genomic and proteomic techniques. We will also investigate the role of these receptors in cell proliferation and calcium signalling. Methods: The mRNAs for NPBWR1 and NPBWR2 were detected using quantitative PCR (qPCR) analysis and further validated by western blot and immunofluorescence analyses. Additionally, we synthesised ligands for these receptors, specifically hNPB (25–53) and hNPW (33–62), to investigate their effects on cell proliferation and intracellular calcium levels in human fibroblasts. Results: Our results demonstrated that hNPW (33–62) has anti-proliferative effect on human dermal fibroblasts and concentration of 0.1-μmol/L can significantly decrease intracellular calcium levels (p < 0.05). Conclusion: This finding suggests a potential role for the NPB/W signalling system in pathologies associated with impaired calcium handling, such as fibrosis. Furthermore, we observed that the proliferation of human fibroblasts was not affected by hNPB (25–53). Our findings could lead to the development of new therapeutic strategies for various skin conditions and improved wound healing.

Here we report a simple electrochemical route towards the synthesis of S-arylated peptides by a site selective coupling of peptides with aryl halides under base free conditions. This approach demonstrates the power of electrochemistry to access highly complex peptides conjugates under mild reaction conditions. We demonstrated also the utility of this appraoch to access to cyclic peptides.