Motor neuron disease articles within Nature Communications

Featured

  • Article
    | Open Access

    GGGGCC repeat expansion in the C9orf72 gene causes amyotrophic lateral sclerosis and frontotemporal dementia. Here the authors show that CCCCGG antisense repeat RNA binds and inhibits phenylalanine-tRNA synthetase resulting in decreased levels of tRNAphe and phenylalanine rich proteins.

    • Mirjana Malnar Črnigoj
    • , Urša Čerček
    •  & Boris Rogelj

  • Article
    | Open Access

    Amyotrophic lateral sclerosis (ALS) is a primary neurodegenerative disease, which is characterized by increased immune cell infiltration of the central nervous system. Here authors show that the phenotypic profile of T cells in the blood and cerebrospinal fluid of newly diagnosed ALS patients can predict disease progression, thus providing evidence that T cells contribute to disease pathology.

    • Solmaz Yazdani
    • , Christina Seitz
    •  & Fang Fang

  • Article
    | Open Access

    Amyotrophic Lateral Sclerosis related TDP-43 protein translocates to stress granules with a concomitant reduction in mobility. Here, the authors use single molecule tracking and find a stress-induced reduction in TDP-43 mobility also in the cytoplasm potentially relevant for TDP-43 aggregation.

    • Lisa Streit
    • , Timo Kuhn
    •  & Karin M. Danzer

  • Article
    | Open Access

    ALS and FTLD are both characterized by insoluble cytoplasmic depositions of TDP43. Here the authors show that the nucleopore protein NUP62 is mislocalized in C9orf72 and sporadic ALS/FTLD and propose that it interacts with TDP-43 to promote its insolubility.

    • Amanda M. Gleixner
    • , Brandie Morris Verdone
    •  & Christopher J. Donnelly

  • Article
    | Open Access

    TDP-43 is a nucleic acid binding protein, whose insoluble aggregates are neuropathological hallmarks of specific subsets of patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Post-translational modifications and acetylation of TDP-43 impact its interaction with RNA, its localization in the cells, and are linked to disease. Using antibodies generated against TDP-43 lysine acetylation sites, sirtuin-1 was found to potently deacetylate amber suppressed [acK136]TDP-43 and reduce its aggregation propensity. Thus, distinct lysine acetylations modulate nuclear import, RNA binding as well as phase separation and aggregation of TDP-43, suggesting regulatory mechanisms for TDP-43 pathogenesis.

    • Jorge Garcia Morato
    • , Friederike Hans
    •  & Philipp J. Kahle

  • Article
    | Open Access

    C9orf72 expansion mutations are the most common genetic cause of ALS and FTD, which have limited therapies. The authors generate stereopure oligonucleotides that selectively deplete expansion-containing transcripts and protect against expansion-associated pathologies in preclinical models.

    • Yuanjing Liu
    • , Jean-Cosme Dodart
    •  & Robert H. Brown Jr.

  • Article
    | Open Access

    Disturbances in IP3 receptor-mediated release of Ca2+ from the endoplasmatic reticulum are associated with neurodegenerative disease. Here, the authors identify in four families with hereditary spastic paraplegia biallelic mutations in RNF170 that associate with increased basal levels of IP3 receptors.

    • Matias Wagner
    • , Daniel P. S. Osborn
    •  & Rebecca Schüle

  • Article
    | Open Access

    MR-focused ultrasound can be used to transiently open the blood-brain barrier (BBB). Here, the authors report the results of a first-in-human trial on four patients with amyotrophic lateral sclerosis (ALS), showing that the procedure reversibly permeabilised the BBB in the motor cortex without complications, and suggest that the procedure could in the future be used to increase drug delivery in ALS patients.

    • Agessandro Abrahao
    • , Ying Meng
    •  & Lorne Zinman

  • Article
    | Open Access

    Although defects in nucleocytoplasmic transport (NCT) may be central to the pathogenesis of ALS, the molecular mechanisms modulating the nuclear pore function are still largely unknown. Here, authors show that genetic and pharmacological modulation of actin polymerization disrupts nuclear pore integrity and can be targeted to rescue nuclear pore instability and dysfunction caused by mutant PFN1 as well as by C9ORF72 repeat expansion

    • Anthony Giampetruzzi
    • , Eric W. Danielson
    •  & Claudia Fallini

  • Article
    | Open Access

    Many Amyotrophic Lateral Sclerosis (ALS)-linked mutations cause accumulation of stress granules, and most ALS cases are caused by repeat expansions in C9ORF72. Here the authors show that C9ORF72 and the autophagy receptor p62 interact to associate with proteins symmetrically dimethylated on arginines such as FUS, to eliminate stress granules by autophagy.

    • Maneka Chitiprolu
    • , Chantal Jagow
    •  & Derrick Gibbings

  • Article
    | Open Access

    Repeat-associated non-AUG (RAN) translation contributes to the pathogenic mechanism of several microsatellite expansion diseases. Here the authors delineate the different steps involved in recruiting the ribosome to initiate G4C2 RAN translation to produce poly-Glycine Alanine, poly-Glycine Proline, and poly-Glycine Arginine repeats.

    • Ricardos Tabet
    • , Laure Schaeffer
    •  & Clotilde Lagier-Tourenne

  • Article
    | Open Access

    Relatives of patients with amyotrophic lateral sclerosis have an unexpectedly high incidence of schizophrenia. Here, the authors show a genetic link between the two conditions, suggesting shared neurobiological mechanisms.

    • Russell L. McLaughlin
    • , Dick Schijven
    •  & Michael C. O’Donovan

  • Article
    | Open Access

    Sensitive and label-free imaging methods to visualize nerve degeneration are currently lacking. Here authors show that stimulated Raman scattering (SRS) microscopy can be used to monitor peripheral nerve degeneration in mouse models of amyotrophic lateral sclerosis (ALS) and in postmortem tissue from ALS patients.

    • Feng Tian
    • , Wenlong Yang
    •  & Kevin Eggan

  • Article
    | Open Access

    The socioeconomic burden of amyotrophic lateral sclerosis (ALS) is high, but the projected number of cases in the upcoming years is unclear. Here, the authors estimate the number and distribution of ALS cases to 2040, and show that cases are projected to increase, particularly in developing nations.

    • Karissa C. Arthur
    • , Andrea Calvo
    •  & Bryan J. Traynor

  • Article
    | Open Access

    SIRTs have been reported to provide neuroprotective actions in polyglutamine diseases, and are linked to the beneficial effects of caloric restrictive diets. Here, the authors show caloric restriction improves behavioural and neuropathological deficits in MJD model mice, an effect dependent on SIRT1 activity.

    • Janete Cunha-Santos
    • , Joana Duarte-Neves
    •  & Cláudia Cavadas

  • Article
    | Open Access

    Ian Blair and colleagues use genome-wide linkage analysis and whole exome sequencing to identify mutations in the CCNF gene in large cohorts of amyotrophic lateral sclerosis and frontotemporal dementia patients. In addition to validating the mutations in international cohorts, the authors also show that mutant CCNFgene product affects ubiquitination and protein degradation in cultured cells.

    • Kelly L. Williams
    • , Simon Topp
    •  & Ian P. Blair

  • Article
    | Open Access

    Nerve damage can lead to skeletal muscle paralysis and atrophy. Here, the authors show that localized photostimulation of mouse calf muscle expressing the light-sensitive channel Channelrhodopsin-2 generates contraction in the absence of neural impulses and prove that this strategy can be used to prevent muscle atrophy.

    • Philippe Magown
    • , Basavaraj Shettar
    •  & Victor F. Rafuse

  • Article
    | Open Access

    Perineuronal astrocyte reactivity is implicated in functional recovery following nerve injury but exactly how this happens is unclear. Tyzack et al. show that perineuronal astrocytes facilitate the recovery of synaptic inputs to damaged neurons via STAT3-dependent upregulation of the astrocytic protein TSP-1.

    • Giulia E. Tyzack
    • , Sergey Sitnikov
    •  & András Lakatos

Browse broader subjects

Browse narrower subjects

Browse Motor neuron disease across other nature.com journals