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 cli Show more
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
Multiple Sclerosis (MS) therapies effectively modulate peripheral immune responses but largely fail to promote neural repair within the central nervous system. This review evaluates whether psychedeli Show more
Multiple Sclerosis (MS) therapies effectively modulate peripheral immune responses but largely fail to promote neural repair within the central nervous system. This review evaluates whether psychedelic compounds (PSYs), via 5-HT2A activation, can fill a critical therapeutic gap: the need for agents that simultaneously suppress neuroinflammation and promote regeneration. We dissect the evidence suggesting PSYs can reprogram the neuroimmune milieu by downregulating key pro-inflammatory cytokines (e.g., TNF-α, IL-6) in glial cells while concurrently upregulating crucial neurotrophic factors (e.g., BDNF) that promote synaptic plasticity and oligodendrocyte support. However, we argue that the current evidence, largely derived from non-specific inflammation models, is insufficient to predict clinical efficacy in an autoimmune disease like MS. We critically analyze the significant translational barriers-from cardiovascular and psychiatric risks to profound legal and ethical challenges-that temper the immediate clinical promise. Finally, we propose a forward-looking perspective, suggesting that the true value of PSYs may lie not in their direct clinical use, but in uncovering novel therapeutic pathways. The emergence of non-hallucinogenic, functionally selective 5-HT2A agonists, inspired by psychedelic pharmacology, represents a more viable strategy to harness these mechanisms for MS therapy, demanding rigorous preclinical validation in disease-relevant models. Show less