Nature Reviews Neurology最新文献

{"title":"Coeliac disease as a model for understanding multiple sclerosis","authors":"Natalia Drosu, Kjetil Bjornevik, Marianna Cortese, Michael Levy, Ludvig M. Sollid","doi":"10.1038/s41582-024-01025-y","DOIUrl":"10.1038/s41582-024-01025-y","url":null,"abstract":"The genetic architecture of multiple sclerosis (MS) is similar to that of coeliac disease, with human leukocyte antigen (HLA) being the greatest genetic determinant in both diseases. Furthermore, similar to the involvement of gluten in coeliac disease, Epstein–Barr virus (EBV) infection is now widely considered to be an important environmental factor in MS. The molecular basis for the HLA association in coeliac disease is well defined, and B cells have a clear role in antigen presentation to gluten-specific CD4+ T cells. By contrast, the mechanisms underlying the HLA association of MS are unknown but accumulating evidence indicates a similar role of B cells acting as antigen-presenting cells. The growing parallels suggest that much could be learned about the mechanisms of MS by using coeliac disease as a model. In this Perspective article, we discuss the insights that could be gained from these parallels and consider the possibility of antiviral treatment against EBV as a therapy for MS that is analogous to the gluten-free diet in coeliac disease. In this Perspective, the authors discuss how our understanding of coeliac disease could provide insights into the mechanisms of multiple sclerosis, the involvement of Epstein–Barr virus and the possibility of antiviral treatment against the virus as a therapy for multiple sclerosis.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 11","pages":"685-690"},"PeriodicalIF":28.2,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic determinants of brain health in ageing","authors":"Eric E. Smith, Geert Jan Biessels, Virginia Gao, Rebecca F. Gottesman, Arthur Liesz, Neal S. Parikh, Costantino Iadecola","doi":"10.1038/s41582-024-01016-z","DOIUrl":"10.1038/s41582-024-01016-z","url":null,"abstract":"Preservation of brain health is a worldwide priority. The traditional view is that the major threats to the ageing brain lie within the brain itself. Consequently, therapeutic approaches have focused on protecting the brain from these presumably intrinsic pathogenic processes. However, an increasing body of evidence has unveiled a previously under-recognized contribution of peripheral organs to brain dysfunction and damage. Thus, in addition to the well-known impact of diseases of the heart and endocrine glands on the brain, accumulating data suggest that dysfunction of other organs, such as gut, liver, kidney and lung, substantially affects the development and clinical manifestation of age-related brain pathologies. In this Review, a framework is provided to indicate how organ dysfunction can alter brain homeostasis and promote neurodegeneration, with a focus on dementia. We delineate the associations of subclinical dysfunction in specific organs with dementia risk and provide suggestions for public health promotion and clinical management. Peripheral organ dysfunction can have considerable effects on brain health, contributing to neurodegeneration and dementia. This Review explores how clinical and subclinical dysfunction of specific organ systems can impact brain health and discusses the implications for dementia prevention.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 11","pages":"647-659"},"PeriodicalIF":28.2,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continuing evolution of migraine-specific therapies — targeting migraine with precision and persistence","authors":"Dimos D. Mitsikostas, Alan Rapoport","doi":"10.1038/s41582-024-01026-x","DOIUrl":"10.1038/s41582-024-01026-x","url":null,"abstract":"Treatment options for migraine have expanded rapidly over the past few years. The latest success in a phase II trial of a new class of drugs for migraine holds the promise of another alternative, with important implications for our understanding of migraine and its clinical management.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 11","pages":"645-646"},"PeriodicalIF":28.2,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disease-modifying therapies for Parkinson disease: lessons from multiple sclerosis","authors":"Lorraine V. Kalia, Angelica Asis, Nathalie Arbour, Amit Bar-Or, Riley Bove, Daniel G. Di Luca, Edward A. Fon, Susan Fox, Ziv Gan-Or, Jennifer L. Gommerman, Un Jung Kang, Eric C. Klawiter, Marcus Koch, Shannon Kolind, Anthony E. Lang, Karen K. Lee, Matthew R. Lincoln, Penny A. MacDonald, Martin J. McKeown, Tiago A. Mestre, Veronique E. Miron, Daniel Ontaneda, Maxime W. C. Rousseaux, Michael G. Schlossmacher, Raphael Schneider, A. Jon Stoessl, Jiwon Oh","doi":"10.1038/s41582-024-01023-0","DOIUrl":"10.1038/s41582-024-01023-0","url":null,"abstract":"The development of disease-modifying therapies (DMTs) for neurological disorders is an important goal in modern neurology, and the associated challenges are similar in many chronic neurological conditions. Major advances have been made in the multiple sclerosis (MS) field, with a range of DMTs being approved for relapsing MS and the introduction of the first DMTs for progressive MS. By contrast, people with Parkinson disease (PD) still lack such treatment options, relying instead on decades-old therapeutic approaches that provide only symptomatic relief. To address this unmet need, an in-person symposium was held in Toronto, Canada, in November 2022 for international researchers and experts in MS and PD to discuss strategies for advancing DMT development. In this Roadmap article, we highlight discussions from the symposium, which focused on therapeutic targets and preclinical models, disease spectra and subclassifications, and clinical trial design and outcome measures. From these discussions, we propose areas for novel or deeper exploration in PD using lessons learned from therapeutic development in MS. In addition, we identify challenges common to the PD and MS fields that need to be addressed to further advance the discovery and development of effective DMTs. Major advances have been made in disease-modifying therapies for multiple sclerosis, but people with Parkinson disease still lack such treatment options. Drawing on discussions from a symposium held in November 2022, this Roadmap proposes areas for exploration in Parkinson disease using lessons learned from therapeutic development in multiple sclerosis.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 12","pages":"724-737"},"PeriodicalIF":28.2,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fluid biomarkers of chronic traumatic brain injury","authors":"Susanna Friberg, Caroline Lindblad, Frederick A. Zeiler, Henrik Zetterberg, Tobias Granberg, Per Svenningsson, Fredrik Piehl, Eric P. Thelin","doi":"10.1038/s41582-024-01024-z","DOIUrl":"10.1038/s41582-024-01024-z","url":null,"abstract":"Traumatic brain injury (TBI) is a leading cause of long-term disability across the world. Evidence for the usefulness of imaging and fluid biomarkers to predict outcomes and screen for the need to monitor complications in the acute stage is steadily increasing. Still, many people experience symptoms such as fatigue and cognitive and motor dysfunction in the chronic phase of TBI, where objective assessments for brain injury are lacking. Consensus criteria for traumatic encephalopathy syndrome, a clinical syndrome possibly associated with the neurodegenerative disease chronic traumatic encephalopathy, which is commonly associated with sports concussion, have been defined only recently. However, these criteria do not fit all individuals living with chronic consequences of TBI. The pathophysiology of chronic TBI shares many similarities with other neurodegenerative and neuroinflammatory conditions, such as Alzheimer disease. As with Alzheimer disease, advancements in fluid biomarkers represent one of the most promising paths for unravelling the chain of pathophysiological events to enable discrimination between these conditions and, with time, provide prediction modelling and therapeutic end points. This Review summarizes fluid biomarker findings in the chronic phase of TBI (≥6 months after injury) that demonstrate the involvement of inflammation, glial biology and neurodegeneration in the long-term complications of TBI. We explore how the biomarkers associate with outcome and imaging findings and aim to establish mechanistic differences in biomarker patterns between types of chronic TBI and other neurodegenerative conditions. Finally, current limitations and areas of priority for future fluid biomarker research are highlighted. Traumatic brain injury can result in long-lasting symptoms and is associated with progressive neurodegenerative and neuroinflammatory pathology, but biomarkers to diagnose and monitor these chronic effects are lacking. Here, Thelin and co-workers summarize the available evidence for fluid biomarker use in chronic traumatic brain injury.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 11","pages":"671-684"},"PeriodicalIF":28.2,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparing for disease-modifying dementia therapies in the UK","authors":"Claudia Cooper, Charles R. Marshall, Jonathan M. Schott, Sube Banerjee","doi":"10.1038/s41582-024-01022-1","DOIUrl":"10.1038/s41582-024-01022-1","url":null,"abstract":"Although lecanemab has been licensed for use in the UK, the systems to deliver this or similar disease-modifying therapies do not exist. These systems need to be developed urgently, but not at the expense of post-diagnostic care.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 11","pages":"641-642"},"PeriodicalIF":28.2,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142235105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NMOSD and MOGAD: an evolving disease spectrum","authors":"Akiyuki Uzawa, Frederike Cosima Oertel, Masahiro Mori, Friedemann Paul, Satoshi Kuwabara","doi":"10.1038/s41582-024-01014-1","DOIUrl":"10.1038/s41582-024-01014-1","url":null,"abstract":"Neuromyelitis optica (NMO) spectrum disorder (NMOSD) is a relapsing inflammatory disease of the CNS, characterized by the presence of serum aquaporin 4 (AQP4) autoantibodies (AQP4-IgGs) and core clinical manifestations such as optic neuritis, myelitis, and brain or brainstem syndromes. Some people exhibit clinical characteristics of NMOSD but test negative for AQP4-IgG, and a subset of these individuals are now recognized to have serum autoantibodies against myelin oligodendrocyte glycoprotein (MOG) — a condition termed MOG antibody-associated disease (MOGAD). Therefore, the concept of NMOSD is changing, with a disease spectrum emerging that includes AQP4-IgG-seropositive NMOSD, MOGAD and double-seronegative NMOSD. MOGAD shares features with NMOSD, including optic neuritis and myelitis, but has distinct pathophysiology, clinical profiles, neuroimaging findings (including acute disseminated encephalomyelitis and/or cortical encephalitis) and biomarkers. AQP4-IgG-seronegative NMOSD seems to be a heterogeneous condition and requires further study. MOGAD can manifest as either a monophasic or a relapsing disease, whereas NMOSD is usually relapsing. This Review summarizes the history and current concepts of NMOSD and MOGAD, comparing epidemiology, clinical features, neuroimaging, pathology and immunology. In addition, we discuss new monoclonal antibody therapies for AQP4-IgG-seropositive NMOSD that target complement, B cells or IL-6 receptors, which might be applied to MOGAD in the near future. This Review summarizes the history and current concepts of neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), including epidemiology, clinical and neuroimaging features and pathophysiology. It also discusses new molecularly targeted therapies for NMOSD that might be also applied to MOGAD in the future.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 10","pages":"602-619"},"PeriodicalIF":28.2,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142175002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adaptive deep brain stimulation shows promise","authors":"Ian Fyfe","doi":"10.1038/s41582-024-01019-w","DOIUrl":"10.1038/s41582-024-01019-w","url":null,"abstract":"","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 10","pages":"569-569"},"PeriodicalIF":28.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hijacked macrophages sustain glioblastoma cells","authors":"Ian Fyfe","doi":"10.1038/s41582-024-01018-x","DOIUrl":"10.1038/s41582-024-01018-x","url":null,"abstract":"","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 10","pages":"569-569"},"PeriodicalIF":28.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Free DNA activates secondary stroke mechanism","authors":"Ian Fyfe","doi":"10.1038/s41582-024-01020-3","DOIUrl":"10.1038/s41582-024-01020-3","url":null,"abstract":"","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"20 10","pages":"569-569"},"PeriodicalIF":28.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}