Nature Reviews Neurology最新文献

Multiple sclerosis: an immune attack on astrocyte-mediated ion and water homeostasis

IF 38.1 1区医学

Nature Reviews Neurology Pub Date : 2025-04-04 DOI: 10.1038/s41582-025-01081-y

Marjo S. van der Knaap, Rogier Min

{"title":"Multiple sclerosis: an immune attack on astrocyte-mediated ion and water homeostasis","authors":"Marjo S. van der Knaap, Rogier Min","doi":"10.1038/s41582-025-01081-y","DOIUrl":"https://doi.org/10.1038/s41582-025-01081-y","url":null,"abstract":"Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. The chain of events that results in demyelinating lesions is not understood, although most theories assume a primary immune attack on myelin. However, the glial cell adhesion molecule GlialCAM, which forms part of a protein complex in astrocytic endfeet that is crucial for brain ion and water homeostasis, was recently identified as a target for autoimmunity in patients with MS. This complex also includes the astrocytic transmembrane protein MLC1, the water channel aquaporin 4 (AQP4) and the potassium channel KIR4.1. Autoimmunity against AQP4 underlies another demyelinating disorder, neuromyelitis optica, and autoimmunity against KIR4.1 has been implicated in a subtype of MS. Genetic defects in any of these proteins cause leukodystrophies with disruption of brain ion and water homeostasis, which is regulated by astrocytes and secondarily affects myelin. In this Perspective, we argue that an immune attack on the ion and water homeostasis machinery in astrocytic endfeet, rather than directly on myelin, is the primary event in MS and that myelin damage is a consequence of astrocyte dysfunction. This hypothesis is supported by pathological studies on tissue from people with MS and has important implications for disease models and therapy targets.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"37 1","pages":""},"PeriodicalIF":38.1,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782398","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}

引用次数: 0

Epigenetic reprogramming of glioblastoma to overcome chemotherapy resistance

IF 38.1 1区医学

Nature Reviews Neurology Pub Date : 2025-04-04 DOI: 10.1038/s41582-025-01083-w

Heather Wood

引用次数: 0

Extracellular vesicles: translational research and applications in neurology

IF 38.1 1区医学

Nature Reviews Neurology Pub Date : 2025-04-03 DOI: 10.1038/s41582-025-01080-z

Apostolos Manolopoulos, Pamela J. Yao, Dimitrios Kapogiannis

{"title":"Extracellular vesicles: translational research and applications in neurology","authors":"Apostolos Manolopoulos, Pamela J. Yao, Dimitrios Kapogiannis","doi":"10.1038/s41582-025-01080-z","DOIUrl":"https://doi.org/10.1038/s41582-025-01080-z","url":null,"abstract":"Over the past few decades, extensive basic, translational and clinical research has been devoted to deciphering the physiological and pathogenic roles of extracellular vesicles (EVs) in the nervous system. The presence of brain cell-derived EVs in the blood, carrying diverse cargoes, has enabled the development of predictive, diagnostic, prognostic, disease-monitoring and treatment-response biomarkers for various neurological disorders. In this Review, we consider how EV biomarkers can bring us closer to understanding the complex pathogenesis of neurological disorders such as Alzheimer disease, Parkinson disease, stroke, traumatic brain injury, amyotrophic lateral sclerosis and multiple sclerosis. We describe how translational research on EVs might unfold bidirectionally, proceeding from basic to clinical studies but also in the opposite direction, with biomarker findings in the clinic leading to novel hypotheses that can be tested in the laboratory. We demonstrate the potential value of EVs across all stages of the therapeutic development pipeline, from identifying therapeutic targets to the use of EVs as reporters in model systems and biomarkers in clinical research. Finally, we discuss how the cargo and physicochemical properties of naturally occurring and custom-engineered EVs can be leveraged as novel treatments and vehicles for drug delivery, potentially revolutionizing neurotherapeutics.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"69 1","pages":""},"PeriodicalIF":38.1,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766380","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}

引用次数: 0

Management of freezing of gait — mechanism-based practical recommendations

IF 38.1 1区医学

Nature Reviews Neurology Pub Date : 2025-04-01 DOI: 10.1038/s41582-025-01079-6

Anouk Tosserams, Alfonso Fasano, Moran Gilat, Stewart A. Factor, Nir Giladi, Simon J. G. Lewis, Caroline Moreau, Bastiaan R. Bloem, Alice Nieuwboer, Jorik Nonnekes

{"title":"Management of freezing of gait — mechanism-based practical recommendations","authors":"Anouk Tosserams, Alfonso Fasano, Moran Gilat, Stewart A. Factor, Nir Giladi, Simon J. G. Lewis, Caroline Moreau, Bastiaan R. Bloem, Alice Nieuwboer, Jorik Nonnekes","doi":"10.1038/s41582-025-01079-6","DOIUrl":"https://doi.org/10.1038/s41582-025-01079-6","url":null,"abstract":"Freezing of gait (FOG) is a debilitating motor symptom that commonly occurs in Parkinson disease, atypical parkinsonism and other neurodegenerative conditions. Management of FOG is complex and requires a multifaceted approach that includes pharmacological, surgical and non-pharmacological interventions. In this Expert Recommendation, we provide state-of-the-art practical recommendations for the management of FOG, based on the latest insights into the pathophysiology of the condition. We propose two complementary treatment flows, both of which are linked to the pathophysiology and tailored to specific FOG phenotypes. The first workflow focuses on the reduction of excessive inhibitory outflow from the basal ganglia through use of dopaminergic medication or advanced therapies such as deep brain stimulation and infusion therapy. The second workflow focuses on facilitation of processing across cerebral compensatory networks by use of non-pharmacological interventions. We also highlight interventions that have potential for FOG but are not supported by sufficient evidence to recommend for clinical application. Our updated recommendations are intended to enable effective symptomatic relief once FOG has developed, but we also consider potential targets for preventive approaches. The recommendations are based on scientific evidence where available, supplemented with practice-based evidence informed by our clinical experience.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"22 1","pages":""},"PeriodicalIF":38.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758089","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}

引用次数: 0

A neuroscientific model of near-death experiences

IF 38.1 1区医学

Nature Reviews Neurology Pub Date : 2025-03-31 DOI: 10.1038/s41582-025-01072-z

Charlotte Martial, Pauline Fritz, Olivia Gosseries, Vincent Bonhomme, Daniel Kondziella, Kevin Nelson, Nicolas Lejeune

{"title":"A neuroscientific model of near-death experiences","authors":"Charlotte Martial, Pauline Fritz, Olivia Gosseries, Vincent Bonhomme, Daniel Kondziella, Kevin Nelson, Nicolas Lejeune","doi":"10.1038/s41582-025-01072-z","DOIUrl":"https://doi.org/10.1038/s41582-025-01072-z","url":null,"abstract":"Near-death experiences (NDEs) are episodes of disconnected consciousness that typically occur in situations that involve an actual or potential physical threat or are perceived as such, and the experiences are characterized by a rich content with prototypical mystical features. Several explanatory theories for NDEs have been proposed, ranging from psychological or neurophysiological to evolutionary models. However, these concepts were often formulated independently, and, owing to the fragmented nature of research in this domain, integration of these ideas has been limited. Lines of empirical evidence from different areas of neuroscience, including non-human studies, studies investigating psychedelic-induced mystical experiences in humans, and research on the dying brain, are now converging to provide a comprehensive explanation for NDEs. In this Review, we discuss processes that might underlie the rich conscious experience in NDEs, mostly focusing on prototypical examples and addressing both the potential psychological mechanisms and neurophysiological changes, including cellular and electrophysiological brain network modifications and alterations in neurotransmitter release. On the basis of this discussion, we propose a model for NDEs that encompasses a cascade of concomitant psychological and neurophysiological processes within an evolutionary framework. We also consider how NDE research can inform the debate on the emergence of consciousness in near-death conditions that arise before brain death.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"28 1","pages":""},"PeriodicalIF":38.1,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736561","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}

引用次数: 0

Knowing the enemy: strategic targeting of complement to treat Alzheimer disease

IF 38.1 1区医学

Nature Reviews Neurology Pub Date : 2025-03-24 DOI: 10.1038/s41582-025-01073-y

Andrea J. Tenner, Tiffany J. Petrisko

{"title":"Knowing the enemy: strategic targeting of complement to treat Alzheimer disease","authors":"Andrea J. Tenner, Tiffany J. Petrisko","doi":"10.1038/s41582-025-01073-y","DOIUrl":"https://doi.org/10.1038/s41582-025-01073-y","url":null,"abstract":"The complement system protects against infection, positively responds to tissue damage, clears cell debris, directs and modulates the adaptive immune system, and functions in neuronal development, normal synapse elimination and intracellular metabolism. However, complement also has a role in aberrant synaptic pruning and neuroinflammation — processes that lead to a feedforward loop of inflammation, injury and neuronal death that can contribute to neurodegenerative and neurological disorders, including Alzheimer disease. This Review provides justification, largely from preclinical mouse models but also from correlates with human tissue and biomarkers, for targeting specific complement components for therapeutic intervention in Alzheimer disease. We discuss promising strategies to slow the progression of cognitive loss with minimal undesired effects. The diverse interactions and functions of complement system components can influence biological processes in the healthy and diseased brain; here, these functions are described as a prerequisite to selecting appropriate, safe and effective therapeutic targets for translation to the clinic.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"57 1","pages":""},"PeriodicalIF":38.1,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695753","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}

引用次数: 0

Bioengineering to address progression in multiple sclerosis

IF 28.2 1区医学

Nature Reviews Neurology Pub Date : 2025-03-17 DOI: 10.1038/s41582-025-01078-7

Ian Fyfe

引用次数: 0

Exploring factors that confer cognitive resilience

IF 28.2 1区医学

Nature Reviews Neurology Pub Date : 2025-03-10 DOI: 10.1038/s41582-025-01077-8

Heather Wood

引用次数: 0

Mechanistic insights into the interaction between epilepsy and sleep 癫痫与睡眠之间相互作用的机制研究

IF 28.2 1区医学

Nature Reviews Neurology Pub Date : 2025-03-10 DOI: 10.1038/s41582-025-01064-z

Laurent Sheybani, Birgit Frauscher, Christophe Bernard, Matthew C. Walker

{"title":"Mechanistic insights into the interaction between epilepsy and sleep","authors":"Laurent Sheybani, Birgit Frauscher, Christophe Bernard, Matthew C. Walker","doi":"10.1038/s41582-025-01064-z","DOIUrl":"10.1038/s41582-025-01064-z","url":null,"abstract":"Epidemiological evidence has demonstrated associations between sleep and epilepsy, but we lack a mechanistic understanding of these associations. If sleep affects the pathophysiology of epilepsy and the risk of seizures, as suggested by correlative evidence, then understanding these effects could provide crucial insight into the basic mechanisms that underlie the development of epilepsy and the generation of seizures. In this Review, we provide in-depth discussion of the associations between epilepsy and sleep at the cellular, network and system levels and consider the mechanistic underpinnings of these associations. We also discuss the clinical relevance of these associations, highlighting how they could contribute to improvements in the management of epilepsy. A better understanding of the mechanisms that govern the interactions between epilepsy and sleep could guide further research and the development of novel approaches to the management of epilepsy. Epidemiological evidence has demonstrated associations between sleep and epilepsy, but we lack a mechanistic understanding of these associations. In this Review, Sheybani et al. consider the associations between epilepsy and sleep at the cellular, network and system levels, the mechanistic underpinnings of these associations and their clinical relevance to the management of epilepsy.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"21 4","pages":"177-192"},"PeriodicalIF":28.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582810","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}

引用次数: 0

Psychosis-causing lesions mapped to a hippocampal circuit

IF 28.2 1区医学

Nature Reviews Neurology Pub Date : 2025-03-10 DOI: 10.1038/s41582-025-01074-x

Heather Wood

引用次数: 0