Gliomas are the most common parenchymal tumors of the central nervous system (CNS). With regard to their still unclear etiology, several recent studies have provided evidence of a new category of pathogenic elements called human endogenous retroviruses (HERVs) which seem to contribute to the evolution and progression of many neurological diseases such as amyotrophic lateral sclerosis (ALS), schizophrenia, chronic inflammatory polyneuropathy (CIDP) and, particularly, multiple sclerosis (MS). In these diseases, HERVs exert effects on cellular processes such as inflammation, proliferation, and migration. In previous studies, we demonstrated that in MS, the human endogenous retrovirus type-W envelope protein (HERV-W ENV) interferes with lesion repair through the activation of microglia (MG), the innate myeloid immune cells of the CNS. Here, we now show that HERV-W ENV is also present in the microglial cells (MG) of the tumor microenvironment (TME) in gliomas. It modulates the behavior of glioblastoma (GBM) cell lines in GBM/MG cocultures by altering their gene expression, secreted cytokines, morphology, proliferation, and migration properties and could thereby contribute to key tumor properties.

Multiple sclerosis (MS), an auto-immune disease of the central nervous system (CNS) with inflammatory and neurodegenerative properties, remains an insufficiently understood disease despite more than 150 years of research. In contrast to diseases from other medical fields such as, for instance, oncology, a description of its clinical and non-clinical features based on readouts such as biomarkers is still in its infancy. While, in this regard, neurofilament light chain (NfL) seems to be a promising new tool, the significant intra- and interindividual variation of this serological marker somewhat limits its widespread applicability in everyday clinical reality. This has sparked novel studies in which glial fibrillary acidic protein (GFAP) was proposed as an on-top marker serving to improve overall specificity. In this context, it was found that MS disease progression was significantly more often associated with increased levels of both NfL and GFAP compared to increased NfL levels alone. This highlights the complexity of the disease while also emphasizing the potential benefits of introducing additional markers to enhance current options. We propose that nitrosative stress markers, such as nitrate, nitrite, and nitrotyrosine (3NT), could serve this purpose effectively.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) of still unclear etiology. In recent years, the search for biomarkers facilitating its diagnosis, prognosis, therapy response, and other parameters has gained increasing attention. In this regard, in a previous meta-analysis comprising 22 studies, we found that MS is associated with higher nitrite/nitrate (NOx) levels in the cerebrospinal fluid (CSF) compared to patients with non-inflammatory other neurological diseases (NIOND). However, many of the included studies did not distinguish between the different clinical subtypes of MS, included pre-treated patients, and inclusion criteria varied. As a follow-up to our meta-analysis, we therefore aimed to analyze the serum and CSF NOx levels in clinically well-defined cohorts of treatment-naïve MS patients compared to patients with somatic symptom disorder. To this end, we analyzed the serum and CSF levels of NOx in 117 patients (71 relapsing–remitting (RR) MS, 16 primary progressive (PP) MS, and 30 somatic symptom disorder). We found that RRMS and PPMS patients had higher serum NOx levels compared to somatic symptom disorder patients. This difference remained significant in the subgroup of MRZ-negative RRMS patients. In conclusion, the measurement of NOx in the serum might indeed be a valuable tool in supporting MS diagnosis.