Microenvironment as a key driver in disorders affecting the central and peripheral nervous systems

The microenvironment – defined as the complex network of cells, signaling molecules, and non-cellular components within a specific tissue – plays a pivotal role not only in maintaining tissue homeostasis, but also in the onset and progression of pathological conditions. This research focused on how the microenvironment impacts diseases affecting the central and peripheral nervous systems. In particular, this work presents two studies that highlight the interconnectedness and essential role of the microenvironment in two challenging conditions: brain tumors and severe gastrointestinal dysmotility (SD). The first study focused on the development and validation of a novel protocol for extracting tumor secretome (i.e. all the secretory factors released by the tumor mass) directly from glioma patients’ tissue, with the goal of advancing the methodological approach to study glioma microenvironment. The tested method not only proved to held promise in enhancing the grasp of glioma biology, but also in uncovering new potential therapeutic targets. On the other hand, the second study aimed to explore the critical impact of microenvironment on SD pathogenesis. Results on SD patients showed how microvascular abnormalities might be a significant contributor to these gastrointestinal motility disorders. Moreover, in vitro findings suggest how vascular alterations could directly impact neuronal function. In summary, this comprehensive and multifaced work advocates for a paradigm shift in treatment strategies, emphasizing the need to focus on microenvironmental interactions to improve clinical outcomes. All in all, the presented work not only reinforces the importance of studying the microenvironment for deciphering disease mechanisms, but also stresses the necessity of developing microenvironment-focused therapies to improve the effectiveness of medical treatments and pave the way for more personalized approaches.