Amyotrophic lateral sclerosis articles within Nature Communications

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  • Article
    | Open Access

    Repeat expansion mutation in C9ORF72 is the most common cause of familial ALS. Here, the authors generate motor neurons from cells of patients with C9ORF72 mutations, and characterize changes in gene expression in these motor neurons compared to genetically corrected lines, which suggest that glutamate receptor subunit GluA1 is dysregulated in this form of ALS.

    • Bhuvaneish T. Selvaraj
    • , Matthew R. Livesey
    •  & Siddharthan Chandran

  • Article
    | Open Access

    Abnormal cytoplasmic aggregates of FUS are a hallmark of some forms of amyotrophic lateral sclerosis (ALS). Here, using neurons derived from patients with FUS-ALS, the authors demonstrate that impairment of PARP-dependent DNA damage signaling is an event that occurs upstream of neurodegeneration and cytoplasmic aggregate formation in FUS-ALS.

    • Marcel Naumann
    • , Arun Pal
    •  & Andreas Hermann

  • 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

    Impaired turnover of TDP-43 by impaired autophagy or proteasomal function have been suggested to be the cause of TDP-43 accumulation, a hallmark of ALS. Here the authors demonstrate that endocytosis is also important for regulating TDP-43 turnover and toxicity.

    • Guangbo Liu
    • , Alyssa N. Coyne
    •  & J. Ross Buchan

  • Article
    | Open Access

    A nucleotide repeat expansion in C9orf72 is a common genetic cause of neurodegenerative disorders. Here, the authors provide insight into the molecular mechanism by which this repeat undergoes Repeat-Associated Non-AUG (RAN) translation, implicating the integrated stress response and eIF2α phosphorylation.

    • Katelyn M. Green
    • , M. Rebecca Glineburg
    •  & Peter K. Todd

  • Article
    | Open Access

    Astrocytes can have protective or detrimental effects on neurons during injury, but the molecular mechanisms that determine these different states are unresolved. Here the authors identify a pathway via neuronal EphB1 that induces neuroprotective signalling in astrocytes through ephrin-B1 mediated STAT3 activation, which is impaired in models of amyotrophic lateral sclerosis.

    • Giulia E. Tyzack
    • , Claire E. Hall
    •  & András Lakatos

  • Article
    | Open Access

    Amyotrophic lateral sclerosis (ALS) leads to selective loss of motor neurons. Using motor neurons derived from induced pluripotent stem cells from patients with ALS and FUS mutations, the authors demonstrate that axonal transport deficits that are observed in these cells can be rescued by HDAC6 inhibition.

    • Wenting Guo
    • , Maximilian Naujock
    •  & Ludo Van Den Bosch

  • Article
    | Open Access

    The RNA for ALS- and frontotemporal dementia-associated C9ORF72 gene is exported from nucleus via an unknown mechanism. This study shows that reduction of nuclear export adaptor SRSF1 can alleviate neuronal cell death and nuclear export of C9ORF72 inDrosophilaand patient-derived induced motor neurons.

    • Guillaume M. Hautbergue
    • , Lydia M. Castelli
    •  & Pamela J. Shaw

  • Article
    | Open Access

    TDP-43 aggregation is observed in amyotrophic lateral sclerosis. Here the authors combine X-ray crystallography, nuclear magnetic resonance and electron microscopy studies and show that physiological oligomerization of TDP-43 is mediated through its N-terminal domain, which forms functional and dynamic oligomers antagonizing pathologic aggregation.

    • Tariq Afroz
    • , Eva-Maria Hock
    •  & Magdalini Polymenidou

  • Article
    | Open Access

    Mutations inCHCHD10 have been recently associated with frontotemporal dementia and amyotrophic lateral sclerosis. Here the authors study the functions of endogenous CHCHD10 in Caenorhabditis elegans, primary neurons, and mouse, and show that it normally protects mitochondria and synaptic integrity, and retains TDP-43 in the nucleus.

    • Jung-A. A. Woo
    • , Tian Liu
    •  & David E. Kang

  • 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

    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 |

    Dominant mutations in the RNA-binding protein FUS/TLS cause amyotrophic lateral sclerosis (ALS), an adult-onset motor neuron degenerative disease. Here, the authors show that ALS-causative FUS/TLS mutations directly bind the SMN and U1-snRNP complexes, producing both loss and gain of function effects on RNA processing.

    • Shuying Sun
    • , Shuo-Chien Ling
    •  & Don W. Cleveland

  • Article
    | Open Access

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects spinal cord motor neurons. Here the authors use induced pluripotent stem cell-derived motor neurons obtained from patients with ALS-linked mutations, and find functional deficits resulting from a progressive decrease in voltage-activated Na+ and K+currents that occur in the absence of cell death.

    • Anna-Claire Devlin
    • , Karen Burr
    •  & Gareth B. Miles

  • Article |

    The nuclear protein TDP-43 is implicated in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. Here, Cohen et al. discover lysine acetylation as a modification that regulates TDP-43 function, providing a mechanism that could be implicated in the pathogenesis of TDP-43 proteinopathies.

    • Todd J. Cohen
    • , Andrew W. Hwang
    •  & Virginia M. Y. Lee

  • Article |

    Abnormal accumulation of the RNA-binding protein FUS and mutations within the FUS gene have been found in association with amyotrophic lateral sclerosis (ALS). Here, Dini Modigliani et al.uncover a FUS regulatory circuit that implicates the microRNAs miR-141 and miR-200a in a feedback loop disrupted by an ALS-associated mutation.

    • Stefano Dini Modigliani
    • , Mariangela Morlando
    •  & Irene Bozzoni

  • Article
    | Open Access

    Mutations of the SOD1gene are implicated in neurodegenerative diseases such as amyotrophic lateral sclerosis. Wright and colleagues find that SOD1 aggregation in cells is arrested by compounds that bind at the core of SOD1 aggregates, rather than at the dimer interface site.

    • Gareth S.A. Wright
    • , Svetlana V. Antonyuk
    •  & S Samar Hasnain

  • Article |

    The mislocalization and downregulation of the proteins TDP-43 and ADAR2, respectively, are implicated in amyotrophic lateral sclerosis pathology. Yamashita et al. find that downregulation of ADAR2 results in calcium-permeable AMPA receptor-mediated calpain activation and subsequent aberrant cleavage of TDP-43.

    • Takenari Yamashita
    • , Takuto Hideyama
    •  & Shin Kwak

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