98%
921
2 minutes
20
Multiple sclerosis (MS) is a multifaceted, chronic neuroinflammatory condition of the central nervous system (CNS) marked by demyelination, gliosis, and axonal degradation. Despite the comprehensive investigation, the exact etiology remains unclear, requiring complex interactions among genetic, epigenetic, and environmental variables. This review highlights the pressing necessity to integrate emerging evidence connecting genetic predisposition, specifically HLA-DRB1*15:01 and over 200 non-HLA variants, with alterable environmental factors, including Epstein-Barr virus (EBV) infection, vitamin D deficiency, smoking, obesity, and heavy metal exposure. The study underscores the distinct gender-specific and geographical patterns of disease frequency and elucidates the immunological changes during pregnancy and adolescence that influence disease progression. The article methodologically synthesizes data from genome-wide association studies, experimental autoimmune encephalomyelitis models, and epidemiological cohorts, integrating these with technological advancements including neuroimaging, biosensor development, and AI-driven analytics. It examines the pathophysiological consequences of heavy metals, highlighting their involvement in mitochondrial dysfunction, oxidative stress, and neuroinflammation. The paper delineates the transformational potential of nanotherapeutics, extracellular vesicles, and artificial intelligence in improving early diagnostics, medication administration, and tailored treatment approaches. The review presents MS as a disease continuum, advocating for a paradigm shift in its classification and management. Additionally, this review offers a comprehensive viewpoint by integrating immunogenetics with digital medicine and novel medicines, potentially informing future diagnostic and therapeutic advancements. The study emphasizes the imperative of amalgamating genetic, environmental, and computational knowledge to enhance precision therapy in MS.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.brainres.2025.149844 | DOI Listing |
Sci Transl Med
September 2025
Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., 4070 Basel, Switzerland.
Oligodendrocytes, the myelinating cells of the central nervous system (CNS), are essential for the formation of myelin sheaths and pivotal for maintaining axonal integrity and conduction. Disruption of these cells and the myelin sheaths they produce is a hallmark of demyelinating conditions like multiple sclerosis or those resulting from certain drug side effects, leading to profound neurological impairments. In this study, we created a human brain organoid comprising neurons, astrocytes, and myelinating oligodendrocytes.
View Article and Find Full Text PDFSci Transl Med
September 2025
Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
IFN-β, a type I interferon, has been used as a first-line therapy for patients with multiple sclerosis (MS) for more than 30 years; however, the cellular and molecular basis of its therapeutic efficacy remains unclear. Here, we first used experimental autoimmune encephalomyelitis (EAE), a mouse model for MS, to show that the therapeutic effects of IFN-β were associated with a down-regulation of microRNA-21 (miR-21) and pathogenic T17 (pT17) cells. In vitro experiments demonstrated that genetic knockout of miR-21 directly inhibited pathogenic T17 cell differentiation.
View Article and Find Full Text PDFAmyotroph Lateral Scler Frontotemporal Degener
September 2025
Department of Physiotherapy and Laboratory for Technological Innovation in Health, Federal University of Rio Grande do Norte, Natal, Brazil.
Fatigue remains a poorly understood symptom in individuals with ALS, and little is known about its associtation with other symptoms, including functional impairment, cognition, and pain. To identify the levels of fatigue, pain, ALSFRS-R, and cognition of a Brazilian group of individuals with ALS, in order to verify possible influences between these symptoms and fatigue. This is a cross-sectional study conducted with individuals with ALS who were recruited intentionally, using a non-probabilistic sampling method.
View Article and Find Full Text PDFMult Scler
September 2025
Neuroimaging Unit, Neuroimmunology Division, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA; Department of Neurology, VA Medical Center, TN Valley Healthcare System, Nashville, TN, USA.
Background: There is limited knowledge on the post-glymphatic structures such as the parasagittal dural (PSD) space and the arachnoid granulations (AGs) in multiple sclerosis (MS).
Objectives: To evaluate differences in volume and macromolecular content of PSD and AG between people with newly diagnosed MS (pwMS), clinically isolated syndrome (pwCIS), or radiologically isolated syndrome (pwRIS) and healthy controls (HCs) and their associations with clinical and radiological disease measures.
Methods: A total of 69 pwMS, pwCIS, pwRIS, and HCs underwent a 3.
Alpha Psychiatry
August 2025
Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, 130021 Changchun, Jilin, China.
Background: The progressive legalization and widespread use of cannabis has led to its use as a treatment for certain neuropsychiatric disorders. Traditional epidemiological studies suggest that cannabis use has an effect on some neurocognitive aspects. However, it is unclear whether cannabis use is causally related to common neuropsychiatric disorders.
View Article and Find Full Text PDF