Featured
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In Brief |
α-Synuclein seeds in amyotrophic lateral sclerosis
New evidence that α-synuclein can contribute to the pathogenesis of amyotrophic lateral sclerosis has come from analysis of cerebrospinal fluid.
- Ian Fyfe
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Correspondence |
Questioning the cycad theory of Kii ALS–PDC causation
- Yasumasa Kokubo
- , Satoru Morimoto
- & Mari Yoshida
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Review Article |
Biomarkers in amyotrophic lateral sclerosis: current status and future prospects
This Review describes the emerging landscape of diagnostic, categorical and pharmacodynamic biomarkers for amyotrophic lateral sclerosis and considers the role of these biomarkers in the rapidly evolving landscape of new therapeutics for this condition.
- Roisin McMackin
- , Peter Bede
- & Orla Hardiman
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Review Article |
The amyotrophic lateral sclerosis exposome: recent advances and future directions
The amyotrophic lateral sclerosis exposome is the lifetime accumulation of environmental exposures that increase disease risk and affect progression. This Review summarizes the literature that has sought to characterize aspects of the amyotrophic lateral sclerosis exposome and considers potential mechanisms of exposure-induced toxicity.
- Stephen A. Goutman
- , Masha G. Savelieff
- & Eva L. Feldman
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Research Highlight |
New mechanistic insights into TDP-43 pathology
Two new studies have provided important mechanistic insights into TDP-43 pathology, a hallmark of neurodegenerative conditions such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration.
- Heather Wood
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Review Article |
Nutritional and metabolic factors in amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease classically thought to impact the motor system, but research is now investigating the contribution of non-motor symptoms. Here, the authors explore evidence that highlights the extent to which nutrition and metabolism might contribute to ALS pathogenesis, and discuss the effectiveness of modifying energy balance in ALS.
- Albert Ludolph
- , Luc Dupuis
- & Christopher McDermott
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Research Highlight |
Hypothalamic hormone linked to weight loss in ALS
A new study indicates loss of hypothalamic melanin-concentrating hormone in ALS, providing insights into the mechanisms underlying weight loss in individuals with the disease.
- Lisa Kiani
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Research Highlight |
Neuroinflammation in spinal muscular atrophy
A new study reports upregulation of pro-inflammatory cytokines and neurotrophic factors in the cerebrospinal fluid of individuals with a severe form of spinal muscular atrophy.
- Heather Wood
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Review Article |
Prospects for gene replacement therapies in amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS) is a devastating, incurable disease characterized by progressive loss of upper and lower motor neurons. Here, the authors describe the current landscape of genetic therapies for ALS and discuss new opportunities for gene replacement therapy, focusing on loss-of-function mutations.
- Ilaria Giovannelli
- , Adrian Higginbottom
- & Pamela J. Shaw
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Research Highlight |
FTD–ALS risk factors converge on the endolysosomal pathway
New research shows that variants in two FTD–ALS risk genes impair the functioning of the endolysosomal pathway, leading to pathological intracellular accumulation of TDP43 protein.
- Heather Wood
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News & Views |
Monitoring disease onset in amyotrophic lateral sclerosis
A new longitudinal study involving carriers of amyotrophic lateral sclerosis (ALS)-associated mutations has identified a prodromal phase of ALS characterized by mild motor impairment. The findings could help us to define a time window during which neuroprotective interventions might be effective in patients with genetic forms of ALS.
- Mamede de Carvalho
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Review Article |
Nuclear pore complexes — a doorway to neural injury in neurodegeneration
In this Review, Coyne and Rothstein discuss disruptions to the nuclear pore complex and nucleocytoplasmic transport, which are emerging as pathological mechanisms in multiple neurodegenerative diseases, and consider the effects of these changes on cellular function and their potential for therapeutic targeting.
- Alyssa N. Coyne
- & Jeffrey D. Rothstein
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News & Views |
Amyotrophic lateral sclerosis — insight into susceptibility
The largest genome-wide association study of amyotrophic lateral sclerosis to date has identified new risk loci and provided insight into factors that influence susceptibility to the disease, highlighting the possibility that disease risk and disease progression are influenced by separate factors, with therapeutic implications.
- Tiffany W. Todd
- & Leonard Petrucelli
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In Brief |
Levosimendan fails to improve respiratory function in amyotrophic lateral sclerosis
- Heather Wood
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In Brief |
TP73 variants implicate apoptosis in amyotrophic lateral sclerosis pathogenesis
- Heather Wood
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Research Highlight |
Novel genetic form of amyotrophic lateral sclerosis reveals metabolic mechanism and therapeutic target
- Ian Fyfe
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Review Article |
Improving clinical trial outcomes in amyotrophic lateral sclerosis
The identification of pathogenic targets in amyotrophic lateral sclerosis means that effective therapies are increasingly likely. In this Review, Kiernan et al. discuss advances towards therapy and the innovations needed in clinical trials to facilitate the translation into treatments for patients.
- Matthew C. Kiernan
- , Steve Vucic
- & Martin R. Turner
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Comment |
Spinal muscular atrophy — the dawning of a new era
The introduction of therapies for spinal muscular atrophy (SMA) has rapidly changed the clinical landscape, transforming SMA from a lethal to a treatable disease. This transformation has driven further advances, from population screening imperatives to novel treatment delivery approaches, while uncovering health disparities and fuelling debate regarding drug pricing.
- Michelle A. Farrar
- & Matthew C. Kiernan
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News & Views |
Spinal muscular atrophy — challenges in the therapeutic era
With the advent of disease-modifying therapies for spinal muscular atrophy, prenatal and extra-neural alterations associated with the condition have garnered increasing attention as potential determinants of the therapeutic window and efficacy of novel drugs. Two recent studies highlight the impact of spinal muscular atrophy on prenatal bone and organ development.
- Irene Faravelli
- & Stefania Corti
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Research Highlight |
Synaptotagmin 13 — the key to cell resilience in motor neuron disease?
- Ian Fyfe
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In Brief |
Arginine dimethylation is increased in patients with ALS and can predict disease progression
- Rebecca Kelsey
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News & Views |
Amyotrophic lateral sclerosis — a multisystem neurodegenerative disorder
Amyotrophic lateral sclerosis (ALS) is a progressive motor disorder, and many patients also show non-motor symptoms including executive, behavioural and language dysfunction. A new study demonstrates a robust relationship between progression of these non-motor symptoms and declining motor disease in patients with ALS, providing important insights into mechanisms of ALS pathogenesis.
- Murray Grossman
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In Brief |
A potential biomarker strategy to monitor treatment response in spinal muscular atrophy
- Heather Wood
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Review Article |
C9orf72-mediated ALS and FTD: multiple pathways to disease
Repeat expansions in the C9orf72 gene are a frequent cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Balendra and Isaacs review the pathological and mechanistic features of C9orf72-associated ALS and FTD, highlighting loss-of-function, gain-of-function and downstream mechanisms.
- Rubika Balendra
- & Adrian M. Isaacs
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Review Article |
Genotype–phenotype links in frontotemporal lobar degeneration
Frontotemporal lobar degeneration (FTLD) is a highly heterogeneous group of neurodegenerative diseases. This Review considers the phenotypic and genotypic differences among those with the most common form of FTLD—characterized by TDP43 pathology—with a view to improve patient care and facilitate current efforts to identify effective therapies for these individuals.
- Sara Van Mossevelde
- , Sebastiaan Engelborghs
- & Christine Van Broeckhoven
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News & Views |
CRISPR expands insight into the mechanisms of ALS and FTD
An incomplete grasp of how the G4C2 repeat expansion in C9orf72 leads to amyotrophic lateral sclerosis and frontotemporal dementia has hindered progress in treatment development. Now, a study has combined unbiased genetic screens and CRISPR–Cas9 gene editing to validate known molecular pathways and identify novel therapeutic targets involved in G4C2 repeat pathogenesis.
- Sarah Pickles
- & Leonard Petrucelli
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Research Highlight |
C9orf72 insufficiency cooperates with toxic repeat peptides to kill neurons
- Charlotte Ridler
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Review Article |
Advances in therapy for spinal muscular atrophy: promises and challenges
Approval of the first disease-modifying therapy for spinal muscular atrophy (SMA), the antisense oligonucleotide nusinersen, represents a major breakthrough in neurodegenerative disease research but also has important medical, ethical and financial implications for SMA and beyond. This Review considers the current and future landscape for SMA therapy and the challenges and opportunities that are emerging.
- Ewout J. N. Groen
- , Kevin Talbot
- & Thomas H. Gillingwater
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Brain–body mechanisms contribute to sexual dimorphism in amyotrophic lateral sclerosis
Macrophages — new targets in ALS?
Konzo outbreak in Zambia linked to cassava-based diet
MicroRNA from dying neurons triggers astrocytosis in ALS
Stars of neurology meet at AAN 2018
Reactive microglia protect neurons in ALS
Benefits of nusinersen extend to later-onset SMA
TDP pathology leads to nuclear disruption