The neutrophils extracellular traps (NETs) are a meshwork of chromatin, histonic and non-histonic proteins, and microbicidal agents spread outside the cell by a series of nuclear and cytoplasmic events, collectively called NETosis. NETosis, initially only considered a defensive/apoptotic mechanism, is now considered an extreme defensive solution, which in particular situations induces strong negative effects on tissue physiology, causing or exacerbating pathologies as recently shown in NETs-mediated organ damage in COVID-19 patients. The positive effects of NETs on wound healing have been linked to their antimicrobial activity, while the negative effects appear to be more common in a plethora of pathological conditions (such as diabetes) and linked to a NETosis upregulation. Recent evidence suggests there are other positive physiological NETs effects on wound healing that are worthy of a broader research effort.

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are persistent environmental pollutants, raising concerns due to their widespread presence and disruptive biological effects. These compounds are highly stable, allowing them to bioaccumulate in the environment and living organisms, potentially impacting critical physiological functions such as hormonal balance, immune response, and increasing cancer risk. Despite regulatory restrictions, their pervasive nature necessitates further research into their potential effects on cellular and neuronal function. This study first evaluated the cytotoxic effects of PFOS and PFOA on S1 neuroblastoma cells; a dose-dependent reduction in cell viability was revealed for PFOS, while PFOA exhibited minimal toxicity until millimolar concentrations. We further investigated their potential to modulate GABAergic neurotransmission using patch-clamp electrophysiology. Both PFOS and PFOA caused a significant but reversible reduction in GABA receptor-mediated currents following one-minute pre-treatment. These findings suggest that PFOS and PFOA can interfere with both cellular viability and GABAergic signaling, providing critical insights into their functional impacts and highlighting the need for further investigation into the long-term consequences of PFAS exposure on nervous system health.

Gravity is a primary physical force that has a profound influence on the stability of the cell cytoskeleton. In our research, we investigated the influence of microgravity on altering the cytoskeletal pathways of glioblastoma cells. The highly infiltrative behavior of glioblastoma is supported by cytoskeletal dynamics and surface proteins that allow glioblastoma cells to avoid stable connections with the tissue environment and other cells. Glioblastoma cell line C6 was exposed to a microgravity environment for 24, 48, and 72 h by 3D-RPM, a laboratory instrument recognized to reproduce the effect of microgravity in cell cultures. The immunofluorescence for GFAP, vinculin, and Connexin-43 was investigated as signals related to cytoskeleton dynamics. The polymerization of GFAP and the expression of focal contact structured by vinculin were found to be altered, especially after 48 and 72 h of microgravity. Connexin-43, involved in several intracellular pathways that critically promote cell motility and invasion of glioma cells, was found to be largely reduced following microgravity exposure. In conclusion, microgravity, by reducing the expression of Connexin-43, alters the architecture of specific cytoskeletal elements such as GFAP and increases the focal contact, which can induce a reduction in glioma cell mobility, thereby inhibiting their aggressive metastatic behavior.

Per- and polyfluoroalkyl substances are persistent environmental contaminants increasingly implicated in neurotoxicity. Establishing causality and mechanisms relevant to Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis requires human-relevant systems that capture exposure, barrier function, and brain circuitry. We review advanced cellular platforms—iPSC-derived neuronal and glial cultures, cerebral and midbrain organoids, and chip-based microphysiological systems—that model disease-relevant phenotypes (Aβ/tau pathology, dopaminergic vulnerability, myelination defects) under controlled PFAS exposures and defined genetic risk backgrounds. Modular, fluidically coupled BBB-on-chip → brain-organoid microphysiological systems have been reported, enabling chronic, low-dose PFAS perfusion under physiological shear, real-time barrier integrity readouts such as transepithelial/transendothelial electrical resistance (TEER), quantification of PFAS partitioning and translocation, and downstream neuronal–glial responses assessed by electrophysiology and multi-omics. Across platforms, convergent PFAS-responsive processes emerge—mitochondrial dysfunction and oxidative stress, lipid/ceramide dysregulation, neuroinflammatory signaling, and synaptic/network impairments—providing a mechanistic scaffold for biomarker discovery and gene–environment interrogation with isogenic lines. We outline principles for exposure design (environmentally relevant ranges, longitudinal paradigms), multimodal endpoints (omics, electrophysiology, imaging), and cross-lab standardization to improve comparability. Together, these models advance the quantitative evaluation of PFAS neurotoxicity and support translation into risk assessment and therapeutic strategies.

Alzheimer’s disease (AD) is one of the most widespread neurodegenerative disorders, primarily affecting individuals over the age of 65. It is characterized by severe cognitive impairment, memory loss, difficulties in performing daily activities, ventricular enlargement, and ultimately, dementia. AD is associated with the accumulation of amyloid $\beta \left(A\beta \right)$ protein plaques, intracellular neurofibrillary tangles (NFTs), progressive inflammation, and impairment of both synaptic transmission and mitochondrial function. Due to the limited diagnostic tools available for detecting the disease in its early stages, proteomic biomarkers have gained paramount importance, as they can monitor prodromal molecular alterations linked to AD. Furthermore, proteomic biomarkers can facilitate the longitudinal assessment of disease progression and contribute to the development of personalized therapeutic strategies before the devastating onset of dementia. Research has primarily focused on identifying proteomic biomarkers in cerebrospinal fluid (CSF) and plasma, as discussed in this review, but also in alternative matrices such as saliva and urine. These studies highlight both the high potential of proteomic approaches and the ongoing challenge of identifying clinically available, sensitive, and specific biomarkers for the various stages of the disease.

Alzheimer’s disease (AD) is one of the most widespread neurodegenerative diseases affecting people averaging over 65 years. It manifests with severe cognitive damage, loss of memory, impairment in performing activities, ventricular expansion and final dementia. AD is associated with the deposit of amyloid β protein (Aβ) plaques, intracellular neurofibrillary tangles (NFTs), progressive inflammation and impairment of synaptic transmission and of mitochondrial function. Due to the poor diagnostic tools for the early stages of the disease, proteomics biomarkers have gained a paramount role because they can monitor the prodromal variations of the disease-linked molecular changes. Further, proteome biomarkers can help the follow up of AD progression over time and aid in setting personalized medical care, before the catastrophic consequences of dementia occurs. Research has focused on the identification of proteome biomarkers in cerebrospinal fluid (CSF) and plasma, which are discussed in the present review, but also in other matrices, as saliva and urine, revealing the high potentiality of proteomics approach and, at the same time, the difficulty to identify, for the different stages of the disease, sensitive and specific biomarkers clinically available.