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Structural switch in acetylcholine receptors in developing muscle
Structures of fetal and adult muscle acetylcholine receptors reveal a developmental switch that alters channel biophysics and pharmacology to enable neuromuscular junction maturation, uncovering pathogenic mechanisms underlying congenital myasthenic syndromes.
- Huanhuan Li
- , Jinfeng Teng
- & Ryan E. Hibbs
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Structural insights into vesicular monoamine storage and drug interactions
Monoamines and neurotoxicants share a binding pocket in VMAT1 featuring polar sites for specificity and a wrist-and-fist shape for versatility, and monoamine enrichment in storage vesicles arises from dominant import via favoured lumenal-open transition of VMAT1 and protonation-precluded binding during its cytoplasmic-open transition.
- Jin Ye
- , Huaping Chen
- & Weikai Li
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Article
| Open AccessA model of human neural networks reveals NPTX2 pathology in ALS and FTLD
A neural stem cell culture system derived from induced pluripotent stem cells forms a network of synaptically connected and electrophysiologically active neurons that were used as a model system to identify a mechanism of TDP-43-induced neurodegeneration.
- Marian Hruska-Plochan
- , Vera I. Wiersma
- & Magdalini Polymenidou
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Article
| Open Accessm1A in CAG repeat RNA binds to TDP-43 and induces neurodegeneration
TDP-43 binds to N1-methyladenosine on CAG repeat RNA, resulting in the formation of gel-like TDP-43 aggregates in the cytoplasm that resemble those observed in neurological disease pathology.
- Yuxiang Sun
- , Hui Dai
- & Yinsheng Wang
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Article |
A high-performance neuroprosthesis for speech decoding and avatar control
A study using high-density surface recordings of the speech cortex in a person with limb and vocal paralysis demonstrates real-time decoding of brain activity into text, speech sounds and orofacial movements.
- Sean L. Metzger
- , Kaylo T. Littlejohn
- & Edward F. Chang
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Article
| Open AccessWalking naturally after spinal cord injury using a brain–spine interface
A reliable digital bridge restored communication between the brain and spinal cord and enabled natural walking in a participant with spinal cord injury.
- Henri Lorach
- , Andrea Galvez
- & Grégoire Courtine
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Article |
Autonomous rhythmic activity in glioma networks drives brain tumour growth
A population of highly interconnected cells in glioblastoma makes these tumours resistant to general damage but vulnerable to targeted disruption of this small fraction of cells and their rhythmic Ca2+ oscillations.
- David Hausmann
- , Dirk C. Hoffmann
- & Frank Winkler
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Article
| Open AccessStroke genetics informs drug discovery and risk prediction across ancestries
A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.
- Aniket Mishra
- , Rainer Malik
- & Stephanie Debette
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Article |
Somatic genomic changes in single Alzheimer’s disease neurons
Analyses of single-cell whole-genome sequencing data show that somatic mutations are increased in the brain of individuals with Alzheimer’s disease compared to neurotypical individuals, with a pattern of genomic damage distinct from that of normal ageing.
- Michael B. Miller
- , August Yue Huang
- & Christopher A. Walsh
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Article |
Amyloid fibrils in FTLD-TDP are composed of TMEM106B and not TDP-43
Amyloid fibrils extracted from brains of patients with frontotemporal lobar degeneration with TAR DNA-binding-protein immunoreactivity (FTLD-TDP) are made up of transmembrane protein 106B.
- Yi Xiao Jiang
- , Qin Cao
- & David S. Eisenberg
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Article |
Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM
The identification of high-affinity molecular mimicry between the Epstein–Barr virus (EBV) transcription factor EBNA1 and the CNS protein GlialCAM provides a mechanistic link between multiple sclerosis and EBV.
- Tobias V. Lanz
- , R. Camille Brewer
- & William H. Robinson
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Article |
Structures of the σ2 receptor enable docking for bioactive ligand discovery
Crystal structures of the σ2 receptor are determined and used to perform a docking screen of nearly 500 million molecules, identifying σ2-selective ligands and providing insight into the role of σ2 in neuropathic pain.
- Assaf Alon
- , Jiankun Lyu
- & Andrew C. Kruse
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Article |
Kainate receptor modulation by NETO2
The authors report the structures of glutamate-gated kainate receptors in complex with NETO2 in both the resting and the desensitized states and reveal how kainate receptors in the brain are regulated by NETO2.
- Lingli He
- , Jiahui Sun
- & Yan Zhao
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Article |
A lymphocyte–microglia–astrocyte axis in chronic active multiple sclerosis
Single-nucleus transcriptomics defines a diverse set of immune and glial cells at the chronically inflamed leading edge of demyelinated white matter lesions in patients with multiple sclerosis.
- Martina Absinta
- , Dragan Maric
- & Daniel S. Reich
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Article |
PIK3CA and CCM mutations fuel cavernomas through a cancer-like mechanism
Aggressive cerebral cavernous malformations (CCMs) are found to grow through a three-hit cancer-like mechanism, involving gain of function of a gene that promotes vascular growth, and loss of function of genes that suppress it.
- Aileen A. Ren
- , Daniel A. Snellings
- & Mark L. Kahn
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Article |
Olfactory sniffing signals consciousness in unresponsive patients with brain injuries
Odorant-dependent sniff responses predicted the long-term survival rates of patients with severe brain injury, and discriminated between individuals who were unresponsive and in minimally conscious states.
- Anat Arzi
- , Liron Rozenkrantz
- & Noam Sobel
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Article |
APOE4 leads to blood–brain barrier dysfunction predicting cognitive decline
Breakdown of the blood–brain barrier in individuals carrying the ε4 allele of the APOE gene, but not the ε3 allele, increases with and predicts cognitive impairment and is independent of amyloid β or tau pathology.
- Axel Montagne
- , Daniel A. Nation
- & Berislav V. Zlokovic
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Article |
The gut–brain axis mediates sugar preference
Experiments in mice show that a population of neurons in the vagal ganglia respond to the presence of glucose in the gut and connect to neurons in the brainstem, revealing the circuit that underlies the neural basis for the behavioural preference for sugar.
- Hwei-Ee Tan
- , Alexander C. Sisti
- & Charles S. Zuker
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Article |
MAFG-driven astrocytes promote CNS inflammation
Single-cell RNA sequencing of cells from humans with multiple sclerosis and mice with a model of the disease identifies a population of disease-promoting astrocytes in which anti-oxidant and anti-inflammatory proteins are suppressed.
- Michael A. Wheeler
- , Iain C. Clark
- & Francisco J. Quintana
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Article |
ATP13A2 deficiency disrupts lysosomal polyamine export
The lysosomal polyamine transporter ATP13A2 controls the cellular polyamine content, and impaired lysosomal polyamine export represents a lysosome-dependent cell death pathway that may be implicated in ATP13A2-associated neurodegeneration.
- Sarah van Veen
- , Shaun Martin
- & Peter Vangheluwe
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Article |
NLRP3 inflammasome activation drives tau pathology
The authors show that NLRP3 inflammasome is activated in microglia of patients with fronto-temporal dementia and in a mouse model of tau pathology, and that the loss of NLRP3 inflammasome function decreases tau pathology and improves cognition in mice.
- Christina Ising
- , Carmen Venegas
- & Michael T. Heneka
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Article |
Opposing T cell responses in experimental autoimmune encephalomyelitis
Activated clonally expanded CD4+ T cells display specificity to the myelin peptide MOG, whereas clonally expanded CD8+ T cells depend on T cell receptor recognition of unrelated surrogate peptides and have a regulatory function.
- Naresha Saligrama
- , Fan Zhao
- & Mark M. Davis
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Article |
Potential roles of gut microbiome and metabolites in modulating ALS in mice
A study of the functional microbiome in a mouse model of ALS shows that several gut bacteria may modulate the severity of the disease.
- Eran Blacher
- , Stavros Bashiardes
- & Eran Elinav
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Letter |
Altered human oligodendrocyte heterogeneity in multiple sclerosis
Single-nucleus RNA sequencing analysis identifies different subclusters of oligodendroglia in white matter from individuals with multiple sclerosis compared with controls, and these differences may be important for understanding disease progression.
- Sarah Jäkel
- , Eneritz Agirre
- & Gonçalo Castelo-Branco
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Letter |
Transmission of amyloid-β protein pathology from cadaveric pituitary growth hormone
Archived vials of cadaveric human growth hormone contain substantial levels of amyloid-β (Aβ) peptides and can seed Aβ plaques in susceptible mice, suggesting that this material could have transmitted Aβ pathology to humans.
- Silvia A. Purro
- , Mark A. Farrow
- & John Collinge
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Perspective |
LEDs for photons, physiology and food
This Perspective discusses developments in LED-based solid-state lighting for physiological and agricultural applications, and the anticipated benefits in terms of health and productivity.
- P. M. Pattison
- , J. Y. Tsao
- & B. Bugbee
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Letter |
Dopamine enhances signal-to-noise ratio in cortical-brainstem encoding of aversive stimuli
Dopamine in the medial prefrontal cortex modulates behavioural responses to aversive stimuli by increasing the signal-to-noise ratio of neurons projecting to the dorsal periaqueductal grey.
- Caitlin M. Vander Weele
- , Cody A. Siciliano
- & Kay M. Tye
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Article |
Targeted neurotechnology restores walking in humans with spinal cord injury
Spatially selective and temporally controlled stimulation of the spinal cord, together with rehabilitation, results in substantial restoration of locomotor function in humans with spinal cord injury.
- Fabien B. Wagner
- , Jean-Baptiste Mignardot
- & Grégoire Courtine
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Letter |
Human glioblastoma arises from subventricular zone cells with low-level driver mutations
Human neural stem cells from the subventricular zone are identified as the cells of origin that contain the driver mutations for glioblastomas.
- Joo Ho Lee
- , Jeong Eun Lee
- & Jeong Ho Lee
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Review Article |
New approaches for brain repair—from rescue to reprogramming
- Roger A. Barker
- , Magdalena Götz
- & Malin Parmar
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Letter |
The cryo-electron microscopy structure of huntingtin
The structure of huntingtin in complex with an interactor is determined to an overall resolution of 4 Å, paving the way for improved understanding of the cellular functions of this protein.
- Qiang Guo
- , Bin Huang
- & Stefan Kochanek
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Article |
Microglia-derived ASC specks cross-seed amyloid-β in Alzheimer’s disease
Deposition and spreading of amyloid-β pathology in mice requires binding to microglia-released ASC specks.
- Carmen Venegas
- , Sathish Kumar
- & Michael T. Heneka
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Letter |
A somatic mutation in erythro-myeloid progenitors causes neurodegenerative disease
Braf V600E expression in resident macrophage progenitors leads to clonal expansion of ERK-activated microglia, which causes synaptic and neuronal loss in the brain and results in lethal neurodegenerative disease in adult mice.
- Elvira Mass
- , Christian E. Jacome-Galarza
- & Frederic Geissmann
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Letter |
Antisense oligonucleotide therapy for spinocerebellar ataxia type 2
Antisense oligonucleotides against ATXN2 improved motor neuron function and restored firing frequency in cerebellar Purkinje cells in mouse models of spinocerebellar ataxia type 2.
- Daniel R. Scoles
- , Pratap Meera
- & Stefan M. Pulst
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Letter |
Structural variation in amyloid-β fibrils from Alzheimer's disease clinical subtypes
Structural differences in 40- and 42-residue-long amyloid-β fibrils seeded in vitro from the cortical tissue of patients with different clinical subtypes of Alzheimer’s disease suggest that different fibril structures form in different disease variants and with different peptide lengths.
- Wei Qiang
- , Wai-Ming Yau
- & Robert Tycko
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Letter |
A brain–spine interface alleviating gait deficits after spinal cord injury in primates
A wireless brain–spine interface is presented that enables macaques with a spinal cord injury to regain locomotor movements of a paralysed leg.
- Marco Capogrosso
- , Tomislav Milekovic
- & Grégoire Courtine
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Brief Communications Arising |
Collinge et al. reply
- John Collinge
- , Zane Jaunmuktane
- & Sebastian Brandner
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Article |
Astrocyte scar formation aids central nervous system axon regeneration
Sustained delivery of axon-specific growth factors not typically present in spinal cord lesions allows for robust axonal regrowth only if the astrocytic scar is present—a result that questions the prevailing dogma and suggests that astrocytic scarring aids rather than prevents central nervous system axon regeneration post injury.
- Mark A. Anderson
- , Joshua E. Burda
- & Michael V. Sofroniew
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Letter |
Forniceal deep brain stimulation rescues hippocampal memory in Rett syndrome mice
Deep brain stimulation (DBS) of the fimbria–fornix—a region that provides input to the hippocampus—is shown to restore hippocampus-dependent memory and hippocampal long-term potentiation and neurogenesis in a mouse model of Rett syndrome, suggesting that DBS, which is already used in the treatment of several neurological conditions, could be a viable approach to mitigating cognitive impairment in Rett syndrome and other disorders of childhood intellectual disability.
- Shuang Hao
- , Bin Tang
- & Jianrong Tang
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Brief Communications Arising |
Wild-type microglia do not reverse pathology in mouse models of Rett syndrome
- Jieqi Wang
- , Jan Eike Wegener
- & Andrew A. Pieper
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