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Neuron-glia interactions underlie ALS-like axonal cytoskeletal pathology

journal contribution
posted on 2023-05-17, 01:22 authored by Anna KingAnna King, Tracey DicksonTracey Dickson, Catherine BlizzardCatherine Blizzard, Adele WoodhouseAdele Woodhouse, Foster, SS, Chung, RS, James VickersJames Vickers
Amyotrophic lateral sclerosis (ALS) is a devastating disorder involving loss of movement due to degeneration of motor neurons. Studies suggest that in ALS axonal dysfunction precedes the death of motor neurons. Pathologically, ALS is characterized by neurofilamentous swellings (spheroids) within the axons of motor neurons. However, the causes of this axonopathy and possible resulting axonal dysfunction are not known. Using a novel model of cultured mouse motor neurons, we have determined that these neurons are susceptible to proximal axonopathy, which is related to the glial environment. This axonopathy showed remarkable similarity, both morphologically and neurochemically, to spheroids that develop over months in SOD1G93A transgenic mice. Focal ubiquitination, as well as perturbations of neurofilaments and microtubules, occurred in the axonal spheroid-like swellings in vitro, and visualization of mitochondrial dynamics demonstrated that axonopathy resulted in impaired axonal transport. These data provide strong evidence for the involvement of non-neuronal cells in axonal dysfunction in ALS. This cell culture model may be of benefit for the development of therapeutic interventions directed at axonal preservation.

History

Publication title

Neurobiology of Aging: Experimental and Clinical Research

Volume

32

Pagination

459-469

ISSN

0197-4580

Department/School

Menzies Institute for Medical Research

Publisher

Elsevier Science Inc

Place of publication

360 Park Ave South, New York, USA, Ny, 10010-1710

Rights statement

The definitive version is available at http://www.sciencedirect.com

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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