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A global perspective on research advances and future challenges in Friedreich ataxia
IF 38.1 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-03-03 DOI: 10.1038/s41582-025-01065-y
Elisabetta Indelicato, Martin B. Delatycki, Jennifer Farmer, Marcondes C. França, Susan Perlman, Myriam Rai, Sylvia Boesch

Friedreich ataxia (FRDA) is a rare multisystem, life-limiting disease and is the most common early-onset inherited ataxia in populations of European, Arab and Indian descent. In recent years, substantial progress has been made in dissecting the pathogenesis and natural history of FRDA, and several clinical trials have been initiated. A particularly notable recent achievement was the approval of the nuclear factor erythroid 2-related factor 2 activator omaveloxolone as the first disease-specific therapy for FRDA. In light of these developments, we review milestones in FRDA translational and clinical research over the past 10 years, as well as the various therapeutic strategies currently in the pipeline. We also consider the lessons that have been learned from failed trials and other setbacks. We conclude by presenting a global roadmap for future research, as outlined by the recently established Friedreich’s Ataxia Global Clinical Consortium, which covers North and South America, Europe, India, Australia and New Zealand.

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引用次数: 0
Identification of neurons involved in schizophrenia
IF 28.2 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-17 DOI: 10.1038/s41582-025-01067-w
Ian Fyfe
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引用次数: 0
Degeneration decades before disease onset
IF 28.2 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-17 DOI: 10.1038/s41582-025-01069-8
Ian Fyfe
{"title":"Degeneration decades before disease onset","authors":"Ian Fyfe","doi":"10.1038/s41582-025-01069-8","DOIUrl":"10.1038/s41582-025-01069-8","url":null,"abstract":"","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"21 3","pages":"125-125"},"PeriodicalIF":28.2,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434934","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
CNS drug delivery improves chemotherapy
IF 28.2 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-17 DOI: 10.1038/s41582-025-01070-1
Ian Fyfe
{"title":"CNS drug delivery improves chemotherapy","authors":"Ian Fyfe","doi":"10.1038/s41582-025-01070-1","DOIUrl":"10.1038/s41582-025-01070-1","url":null,"abstract":"","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"21 3","pages":"125-125"},"PeriodicalIF":28.2,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434930","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
Parkinson disease pathology can originate in the kidney
IF 28.2 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-17 DOI: 10.1038/s41582-025-01066-x
Lisa Kiani
New research suggests that pathological α-synuclein in Parkinson disease can propagate from kidney to brain.
{"title":"Parkinson disease pathology can originate in the kidney","authors":"Lisa Kiani","doi":"10.1038/s41582-025-01066-x","DOIUrl":"10.1038/s41582-025-01066-x","url":null,"abstract":"New research suggests that pathological α-synuclein in Parkinson disease can propagate from kidney to brain.","PeriodicalId":19085,"journal":{"name":"Nature Reviews Neurology","volume":"21 3","pages":"125-125"},"PeriodicalIF":28.2,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434932","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
Neurogenesis altered by disease and stimulation
IF 28.2 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-17 DOI: 10.1038/s41582-025-01068-9
Ian Fyfe
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引用次数: 0
Moving towards meaningful patient and public engagement
IF 28.2 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-10 DOI: 10.1038/s41582-025-01061-2
Ruth Dobson, Charlotte Kenten, Joanna Brown, Clarissa Giebel, Sube Banerjee, Claudia Cooper
Patient and public involvement and engagement is increasingly mandated in funding applications, yet often remain tokenistic and transitory. Working with patient and public contributors requires investment, thought, care and time. We discuss approaches that aim to increase agency for coresearchers, with the goal of strengthening public confidence and trust in research.
在资金申请中,患者和公众的参与度越来越高,但往往只是象征性的、短暂的。与患者和公众贡献者合作需要投资、思考、关怀和时间。我们讨论了旨在提高核心研究人员的代理权的方法,目的是加强公众对研究的信心和信任。
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引用次数: 0
Nothing about us, without us — establishing a patient and public involvement and engagement group
IF 28.2 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-10 DOI: 10.1038/s41582-025-01063-0
Rachel Horne, Rosemary Phillips, Mohammed A. Rauf
Implementation of patient and public involvement and engagement (PPIE) to enable patients and carers to feel included and equal to healthcare professionals is challenging to do well. Here, leaders of a PPIE group share their lived experience and highlight the importance of addressing the needs of all participants to enable true partnership.
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引用次数: 0
The impact of rare genetic variants on Alzheimer disease
IF 28.2 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-02-04 DOI: 10.1038/s41582-025-01062-1
Lara De Deyn, Kristel Sleegers
Alzheimer disease (AD) is a progressive neurodegenerative disease with a strong genetic component. Although autosomal dominant mutations and common risk variants in AD risk have been extensively studied, the genetic underpinning of polygenic AD remains incompletely understood. Rare variants could elucidate part of the missing heritability in AD. Rare variant research gained momentum with the discovery of a rare variant in TREM2, along with loss-of-function variants in ABCA7 and SORL1, and has come into full bloom in recent years. Not only has the number of rare variant discoveries increased through large-scale whole-exome and genome sequencing studies, improved imputation in genome-wide association studies and increased focus on understudied populations, the number of studies mapping the functional effects of several of these rare variants has also significantly increased, leading to insights in the pathogenesis of AD and drug development. Here we provide a comprehensive overview of the known and novel rare variants implicated in AD risk, highlighting how they shine new light on AD pathophysiology and provide new inroads for drug development. We will review their impact on individual, familial and population levels, and discuss the potential and challenges of rare variants in genetic risk prediction. In this Review, the authors summarize the genetic and epidemiological characteristics of rare variants associated with Alzheimer disease so far, and explore the insights that these variants have provided into the pathogenic mechanisms of the disease.
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引用次数: 0
Imperatives and co-benefits of research into climate change and neurological disease 气候变化和神经疾病研究的必要性和共同利益
IF 38.1 1区 医学 Q1 CLINICAL NEUROLOGY Pub Date : 2025-01-20 DOI: 10.1038/s41582-024-01055-6
Medine I. Gulcebi, Sara Leddy, Katherine Behl, Derk-Jan Dijk, Eve Marder, Mark Maslin, Anna Mavrogianni, Michael Tipton, David J. Werring, Sanjay M. Sisodiya

Evidence suggests that anthropogenic climate change is accelerating and is affecting human health globally. Despite urgent calls to address health effects in the context of the additional challenges of environmental degradation, biodiversity loss and ageing populations, the effects of climate change on specific health conditions are still poorly understood. Neurological diseases contribute substantially to the global burden of disease, and the possible direct and indirect consequences of climate change for people with these conditions are a cause for concern. Unaccustomed temperature extremes can impair the systems of resilience of the brain, thereby exacerbating or increasing susceptibility to neurological disease. In this Perspective, we explore how changing weather patterns resulting from climate change affect sleep — an essential restorative human brain activity, the quality of which is important for people with neurological diseases. We also consider the pervasive and complex influences of climate change on two common neurological conditions: stroke and epilepsy. We highlight the urgent need for research into the mechanisms underlying the effects of climate change on the brain in health and disease. We also discuss how neurologists can respond constructively to the climate crisis by raising awareness and promoting mitigation measures and research — actions that will bring widespread co-benefits.

有证据表明,人为气候变化正在加速,并正在影响全球人类健康。尽管迫切呼吁在环境退化、生物多样性丧失和人口老龄化等额外挑战的背景下处理对健康的影响,但人们对气候变化对特定健康状况的影响仍然知之甚少。神经系统疾病在很大程度上造成了全球疾病负担,气候变化对这些疾病患者可能造成的直接和间接后果令人担忧。不习惯的极端温度会损害大脑的恢复系统,从而加剧或增加对神经系统疾病的易感性。在这个视角中,我们探索气候变化导致的天气模式变化如何影响睡眠-一种必不可少的恢复性人类大脑活动,其质量对神经系统疾病患者很重要。我们还考虑了气候变化对两种常见神经系统疾病:中风和癫痫的普遍和复杂影响。我们强调迫切需要研究气候变化对大脑健康和疾病影响的潜在机制。我们还讨论了神经学家如何通过提高认识和促进缓解措施和研究——这些行动将带来广泛的共同利益——来建设性地应对气候危机。
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引用次数: 0
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Nature Reviews Neurology
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