Pathogenesis of two axonopathies does not require axonal neurofilaments

ABSTRACT Neurofilaments are a major component of the axonal cytoskeleton and their abnormal accumulation is a prominent feature of the cytopathology encountered in several neurodegenerative

diseases1,2,3,4,5,6,7,8. Thus, an attractive and widely held model of pathogenesis involves the participation of disrupted neurofilaments as a common toxic intermediate9,10,11,12,13. Here,

in direct contrast to this hypothesis, we show that two neurodegenerative disease models in the mouse, dystonia musculorum (dt)14,15 and a superoxide dismutase 1 (SOD1)-mediated form of

human motor neuron disease (amyotrophic lateral sclerosis, ALS)16,17, progress with little or no abatement on a transgenic background in which neurofilaments are withheld from the axonal

compartment18. By specifically excluding a necessary role for axonal neurofilaments, our observations redefine the components of the pathogenic pathway leading to axon disruption in these

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FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS AXONAL TDP-43 CONDENSATES DRIVE NEUROMUSCULAR JUNCTION DISRUPTION THROUGH INHIBITION OF LOCAL SYNTHESIS OF NUCLEAR

ENCODED MITOCHONDRIAL PROTEINS Article Open access 25 November 2021 BIMODAL REGULATION OF AXONAL TRANSPORT BY THE GDNF-RET SIGNALLING AXIS IN HEALTHY AND DISEASED MOTOR NEURONS Article Open

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ACKNOWLEDGEMENTS We gratefully acknowledge the excellent technical assistance of T. Crossfield, K.Galloway-Kay, I. Tretjakoff and P. Valera. We also thank the ‘Centre de Microscopie

Electronique de l'Université d'Angers’ and the Department of Neuropathology, MNI, for assistance in electron microscopy and image analysis. We are particularly grateful to J.

Snipes, MNI, for helpful discussions. This investigation was supported through grants from the MRC and MDAC to A.C.P. and from the AFM to J.E. Travel support was provided by an INSERM/FRSQ

award. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * INSERM CJF 97-08 and University of Angers, CHU, 49033, Angers, France J. Eyer * Departments of Medicine and Neuroscience, Ludwig

Institute for Cancer Research, University of California, San Diego, La Jolla, 92093, California, USA D. W. Cleveland * Division of Neuropathology, Department of Pathology, Johns Hopkins

University School of Medicine, Baltimore, 21205, Maryland, USA P. C. Wong * Laboratory of Developmental Biology, Molecular Oncology Group, H-5, Royal Victoria Hospital, McGill University,

687 Pine Avenue West, Montreal, H3A 1A1, Quebec, Canada A. C. Peterson Authors * J. Eyer View author publications You can also search for this author inPubMed Google Scholar * D. W.

Cleveland View author publications You can also search for this author inPubMed Google Scholar * P. C. Wong View author publications You can also search for this author inPubMed Google

Scholar * A. C. Peterson View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to A. C. Peterson. RIGHTS AND PERMISSIONS

Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Eyer, J., Cleveland, D., Wong, P. _et al._ Pathogenesis of two axonopathies does not require axonal neurofilaments. _Nature_

391, 584–587 (1998). https://doi.org/10.1038/35378 Download citation * Received: 18 June 1997 * Accepted: 04 November 1997 * Issue Date: 05 February 1998 * DOI: https://doi.org/10.1038/35378

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