👤 Francesco Sessa

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system, characterized by inflammation, demyelination, gliosis, and neuronal loss. Cognitive disorders are part of the clinical presentation, as well as in the early stages, with a prevalence rate ranging from 40 to 65% and are strictly associated with poor quality of life. In recent years, advances in the field of molecular biomarkers have contributed to improving the accuracy of cognitive diagnosis and to identifying subjects at risk of developing cognitive disorders. By focusing on longitudinal studies, this review aims to elucidate the temporal dynamics and potential predictive value of CSF and serum biomarkers in identifying cognitive decline and monitoring disease progression in MS. A systematic review was conducted using the PRISMA guidelines. 827 studies were identified by searching PubMed, Scopus, and Web of Science between July and August 2025. After screening, 8 studies fulfilled the eligibility criteria and were included. NfL showed heterogeneous results: some studies identified it as a feasible biomarker able to predict cognitive decline, while others did not. GFAP did not show significant correlations. Parvalbumin was longitudinally associated with poorer cognition and greater fatigue. Specific microRNAs (miR-126.3p, miR-9p) were associated with processing speed decline. Higher BDNF levels were linked to cognitive improvement. Other biomarkers (OPN, IL-6, CHI3L1, CXCL13) provided insufficient evidence. Findings add interesting contributions to the complex picture of the pathophysiology underpinning cognitive decline in MS. The most promising direction is the shift toward blood-based biomarkers, due to their minimally invasive nature and potential for clinical applicability, which may enable clinicians to anticipate, monitor, and potentially modify the cognitive trajectory of people living with MS. Show less

Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 × 10 Show less

Cell polarity is induced and maintained by separation of the apical and basolateral domains through specialized cell-cell junctions. The Crumbs protein and its binding partners are involved in formation and stabilization of adherens junctions. In this study, we describe a novel component of the mammalian Crumbs complex, the FERM domain protein EPB41L5, which associates with the intracellular domains of all three Crumbs homologs through its FERM domain. Surprisingly, the same FERM domain is involved in binding to the HOOK domain of MPP5/PALS1, a previously identified interactor of Crumbs. Co-expression and co-localization studies suggested that in several epithelial derived tissues Epb4.1l5 interacts with at least one Crumbs homolog, and with Mpp5. Although at early embryonic stages Epb4.1l5 is found at the basolateral membrane compartment, in adult tissues it co-localizes at the apical domain with Crumbs proteins and Mpp5. Overexpression of Epb4.1l5 in polarized MDCK cells affects tightness of cell junctions and results in disorganization of the tight junction markers ZO-1 and PATJ. Our results emphasize the importance of a conserved Crumbs-MPP5-EPB41L5 polarity complex in mammals. Show less