Acute inflammation is particularly relevant in the pathogenesis of visceral hypersensitivity associated with inflammatory bowel diseases. Glia within the enteric nervous system, as well as within the central nervous system, contributes to neuroplasticity during inflammation, but whether enteric glia has the potential to modify visceral sensitivity following colitis is still unknown. This work aimed to investigate the occurrence of changes in the neuron–glial networks controlling visceral perception along the gut–brain axis during colitis, and to assess the effects of peripheral glial manipulation. Enteric glia activity was altered by the poison fluorocitrate (FC; 10 µmol kg−1 i.p.) before inducing colitis in animals (2,4-dinitrobenzenesulfonic acid, DNBS; 30 mg in 0.25 mL EtOH 50%), and visceral sensitivity, colon damage, and glia activation along the pain pathway were studied. FC injection significantly reduced the visceral hyperalgesia, the histological damage, and the immune activation caused by DNBS. Intestinal inflammation is associated with a parallel overexpression of TRPV1 and S100β along the gut–brain axis (colonic myenteric plexuses, dorsal root ganglion, and periaqueductal grey area). This effect was prevented by FC. Peripheral glia activity modulation emerges as a promising strategy for counteracting visceral pain induced by colitis.

Melanocortin Receptor Accessory Protein 2 (MRAP2) modulates the trafficking and signal transduction of several G-protein-coupled receptors (GPCRs) involved in the control of energy homeostasis, such as Prokineticin receptors (PKRs). They bind the endogenous ligand prokineticin 2 (PK2), a novel adipokine that has an anorexic effect and modulates thermoregulation and energy homeostasis. In the present work, we used biochemical techniques to analyze the mechanism of interaction of MRAP2 with PKR2 and we identified the specific amino acid regions involved in the complex formation. Our results indicate that MRAP2 likely binds to the N-terminal region of PKR2, preventing glycosylation and consequently the correct receptor localization. We also identified a C-terminal region of MRAP2 that is critical for the interaction with PKR2. Consequently, we analyzed the role of the prokineticin transduction system in the regulation of MRAP2 expression in tissues involved in the control of food intake: at the central level, in hypothalamic explants, and at the peripheral level, in adipocytes. We demonstrated the modulation of MRAP2 expression by the prokineticin transduction system.

At present, googling the search terms "COVID-19" and "Functional foods" yields nearly 500,000,000 hits, witnessing the growing interest of the scientific community and the general public in the role of nutrition and nutraceuticals during the COVID-19 pandemic. Many compounds have been proposed as phytotherapics in the prevention and/or treatment of COVID-19. The extensive interest of the general public and the enormous social media coverage on this topic urges the scientific community to address the question of whether which nutraceuticals can actually be employed in preventing and treating this newly described coronavirus-related disease. Recently, the Canadian biotech pharma company "FSD Pharma" received the green light from the Food and Drug Administration to design a proof-of-concept study evaluating the effects of ultramicronized palmitoylethanolamide (PEA) in COVID-19 patients. The story of PEA as a nutraceutical to prevent and treat infectious diseases dates back to the 1970s where the molecule was branded under the name Impulsin and was used for its immunomodulatory properties in influenza virus infection. The present paper aims at analyzing the potential of PEA as a nutraceutical and the previous evidence suggesting its anti-inflammatory and immunomodulatory properties in infectious and respiratory diseases and how these could translate to COVID-19 care.

Objective The objective of this study was to outline the dynamics of prokineticin‐2 pathway in relation to clinical‐pathological features of Parkinson's disease by examining olfactory neurons of patients. Methods Thirty‐eight patients (26 de novo, newly diagnosed) and 31 sex/age‐matched healthy controls underwent noninvasive mucosa brushing for olfactory neurons collection, and standard clinical assessment. Gene expression levels of prokineticin‐2, prokineticin‐2 receptors type 1 and 2, and prokineticin‐2‐long peptide were measured in olfactory neurons by real‐time polymerase chain reaction (PCR); moreover, the prokineticin‐2 protein and α‐synuclein species (total and oligomeric) were quantified by immunofluorescence staining. Results Prokineticin‐2 expression was significantly increased in Parkinson's disease. De novo patients had higher prokineticin‐2 levels, directly correlated with Movement Disorder Society‐Sponsored Revision of the Unified Parkinson Disease Rating Scale (MDS‐UPDRS) part III motor score. In addition, oligomeric α‐synuclein was higher in Parkinson's disease and directly correlated with prokineticin‐2 protein levels. Total α‐synuclein did not differ between patients and controls. Interpretation Prokineticin‐2 is a chemokine showing neuroprotective effects in experimental models of Parkinson's disease, but translational proof of its role in patients is still lacking. Here, we used olfactory neurons as the ideal tissue to analyze molecular stages of neurodegeneration in vivo, providing unprecedented evidence that the prokineticin‐2 pathway is activated in patients with Parkinson's disease. Specifically, prokineticin‐2 expression in olfactory neurons was higher at early disease stages, proportional to motor severity, and associated with oligomeric α‐synuclein accumulation. These data, consistently with preclinical findings, support prokineticin‐2 as a candidate target in Parkinson's disease, and validate reliability of olfactory neurons to reflect pathological changes of the disease. ANN NEUROL 2023;93:196–204

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