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Subject collection: Neurodegenerative Disorders

  • RESEARCH ARTICLE
    Effects of subthalamic deep brain stimulation on striatal metabolic connectivity in a rat hemiparkinsonian model
    Nadine Apetz, Elena Kordys, Mascha Simon, Britta Mang, Markus Aswendt, Dirk Wiedermann, Bernd Neumaier, Alexander Drzezga, Lars Timmermann, Heike Endepols
    Disease Models & Mechanisms 2019 12: dmm039065 doi: 10.1242/dmm.039065 Published 24 May 2019

    Summary: Deep brain stimulation in the subthalamic nucleus in rats with a unilateral dopaminergic lesion established a new functional interhemispheric striatal network.

  • RESEARCH ARTICLE
    Inhibition of the IGF-1–PI3K–Akt–mTORC2 pathway in lipid rafts increases neuronal vulnerability in a genetic lysosomal glycosphingolipidosis
    Tuba Sural-Fehr, Harinder Singh, Ludovico Cantuti-Catelvetri, Hongling Zhu, Michael S. Marshall, Rima Rebiai, Martin J. Jastrzebski, Maria I. Givogri, Mark M. Rasenick, Ernesto R. Bongarzone
    Disease Models & Mechanisms 2019 12: dmm036590 doi: 10.1242/dmm.036590 Published 23 May 2019

    Summary: The authors present a mechanistic model to understand how alterations of the membrane architecture by the progressive accumulation of sphingolipids undermines basic cell function, with potential implications for a variety of genetic sphingolipidoses and adult neurodegenerative conditions.

  • RESEARCH ARTICLE
    Amyotrophic lateral sclerosis mutant TDP-43 may cause synaptic dysfunction through altered dendritic spine function
    Tongcui Jiang, Emily Handley, Mariana Brizuela, Edgar Dawkins, Katherine E. A. Lewis, Rosemary M. Clark, Tracey C. Dickson, Catherine A. Blizzard
    Disease Models & Mechanisms 2019 12: dmm038109 doi: 10.1242/dmm.038109 Published 17 May 2019

    Summary: Loss of synaptic GluR1, and reduced excitability within pyramidal neurons, implicates hypoexcitability and attenuated synaptic function in the pathogenic decline of neuronal function in TDP-43-associated ALS.

  • RESOURCE ARTICLE
    Recapitulating Parkinson's disease pathology in a three-dimensional human neural cell culture model
    Teresa R. Taylor-Whiteley, Christine L. Le Maitre, James A. Duce, Caroline F. Dalton, David P. Smith
    Disease Models & Mechanisms 2019 12: dmm038042 doi: 10.1242/dmm.038042 Published 9 April 2019

    Editor's choice: This study describes a novel 3D cell culture model that recapitulates key features of neuropathology in synucleinopathies, including large, nuclear-associated α-synuclein and ubiquitin-positive inclusions.

  • RESEARCH ARTICLE
    VPS13A is closely associated with mitochondria and is required for efficient lysosomal degradation
    Sandra Muñoz-Braceras, Alba R. Tornero-Écija, Olivier Vincent, Ricardo Escalante
    Disease Models & Mechanisms 2019 12: dmm036681 doi: 10.1242/dmm.036681 Published 22 February 2019

    Summary: VPS13A, which is implicated in chorea-acanthocytosis, is essential for efficient lysosomal degradation, while localized in close association with mitochondria. We propose that inter-organelle communication may be relevant in the pathogenesis of the disease.

  • RESEARCH ARTICLE
    ApoE-associated modulation of neuroprotection from Aβ-mediated neurodegeneration in transgenic Caenorhabditis elegans
    Edward F. Griffin, Samuel E. Scopel, Cayman A. Stephen, Adam C. Holzhauer, Madeline A. Vaji, Ryan A. Tuckey, Laura A. Berkowitz, Kim A. Caldwell, Guy A. Caldwell
    Disease Models & Mechanisms 2019 12: dmm037218 doi: 10.1242/dmm.037218 Published 15 February 2019

    Summary: We report new humanized nematode models of amyloid-beta and apolipoprotein E gene expression, examining readouts for neurodegeneration, behavior, cellular function and survival, to elucidate the relative contributions of the proteins to the underlying pathology of Alzheimer's disease.

  • RESEARCH ARTICLE
    SOD1 activity threshold and TOR signalling modulate VAP(P58S) aggregation via reactive oxygen species-induced proteasomal degradation in a Drosophila model of amyotrophic lateral sclerosis
    Kriti Chaplot, Lokesh Pimpale, Balaji Ramalingam, Senthilkumar Deivasigamani, Siddhesh S. Kamat, Girish S. Ratnaparkhi
    Disease Models & Mechanisms 2019 12: dmm033803 doi: 10.1242/dmm.033803 Published 7 February 2019

    Summary: ALS8/VAPB(P58S) aggregates appear to be cleared by an increase in cellular reactive oxygen species, which, in turn, triggers proteasomal degradation.

  • RESEARCH ARTICLE
    Yeast-model-based study identified myosin- and calcium-dependent calmodulin signalling as a potential target for drug intervention in chorea-acanthocytosis
    Piotr Soczewka, Damian Kolakowski, Iwona Smaczynska-de Rooij, Weronika Rzepnikowska, Kathryn R. Ayscough, Joanna Kaminska, Teresa Zoladek
    Disease Models & Mechanisms 2019 12: dmm036830 doi: 10.1242/dmm.036830 Published 28 January 2019

    Summary: Using the vps13Δ strain, a yeast model of the neurodegenerative disorder chorea-acanthocytosis, we found that its defects can be overcome by reduction of calcineurin activity and/or type-I-myosin activation.

  • RESEARCH ARTICLE
    SUMOylation by SUMO2 is implicated in the degradation of misfolded ataxin-7 via RNF4 in SCA7 models
    Martina Marinello, Andreas Werner, Mariagiovanna Giannone, Khadija Tahiri, Sandro Alves, Christelle Tesson, Wilfred den Dunnen, Jacob-S. Seeler, Alexis Brice, Annie Sittler
    Disease Models & Mechanisms 2019 12: dmm036145 doi: 10.1242/dmm.036145 Published 11 January 2019

    Summary: In spinocerebellar ataxia type 7, SUMOylation contributes to the clearance of mutant ATXN7. SUMO2-modified ATXN7 interacts with the SUMO-dependent ubiquitin ligase RNF4, which polyubiquitinates ATXN7, promoting its proteasomal degradation.

  • RESEARCH ARTICLE
    A transgenic minipig model of Huntington's disease shows early signs of behavioral and molecular pathologies
    Georgina Askeland, Marie Rodinova, Hana Štufková, Zaneta Dosoudilova, Monika Baxa, Petra Smatlikova, Bozena Bohuslavova, Jiri Klempir, The Duong Nguyen, Anna Kuśnierczyk, Magnar Bjørås, Arne Klungland, Hana Hansikova, Zdenka Ellederova, Lars Eide
    Disease Models & Mechanisms 2018 11: dmm035949 doi: 10.1242/dmm.035949 Published 24 October 2018

    Summary: Here, we show that a minipig model of Huntington's disease mimics human neurodegeneration and holds promise for future intervention studies. However, minipig peripheral blood mononuclear cells express no detectable mutant huntingtin, eliminating their use as monitoring tools.

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