DOI: 10.1073/pnas.95.16.9631. Absence of neurofilaments reduces the selective vulnerability of motor neurons and slows disease caused by a familial amyotrophic lateral sclerosis-linked superoxide dismutase 1 mutant

Absence of neurofilaments reduces the selective vulnerability of motor neurons and slows disease caused by a familial amyotrophic lateral sclerosis-linked superoxide dismutase 1 mutant

10.1073/pnas.95.16.9631

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Mutations in superoxide dismutase 1 (SOD1), the only proven cause of amyotrophic lateral sclerosis (ALS), provoke disease through an unidentified toxic property. Neurofilament aggregates are pathologic hallmarks of both sporadic and SOD1-mediated familial ALS. By deleting NF-L, the major neurofilament subunit required for filament assembly, onset and progression of disease caused by familial ALS-linked SOD1 mutant G85R are significantly slowed, while selectivity of mutant-mediated toxicity for motor neurons is reduced. In NF-L-deleted animals, levels of the two remaining neurofilament subunits, NF-M and NF-H, are markedly reduced in axons but are elevated in motor neuron cell bodies. Thus, while neither perikaryal nor axonal neurofilaments are essential for SOD1-mediated disease, the absence of assembled neurofilaments both diminishes selective vulnerability and slows SOD1 G85R mutant-mediated toxicity to motor neurons.

Bibliography

Williamson, T. L., Bruijn, L. I., Zhu, Q., Anderson, K. L., Anderson, S. D., Julien, J.-P., & Cleveland, D. W. (1998). Absence of neurofilaments reduces the selective vulnerability of motor neurons and slows disease caused by a familial amyotrophic lateral sclerosis-linked superoxide dismutase 1 mutant. Proceedings of the National Academy of Sciences, 95(16), 9631â9636.

Authors 7

Toni L. Williamson (first)
Lucie I. Bruijn (additional)
Qinzhang Zhu (additional)
Karen L. Anderson (additional)
Scott D. Anderson (additional)
Jean-Pierre Julien (additional)
Don W. Cleveland (additional)

References 61 Referenced 175

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:42 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 4:42 p.m.)
Indexed	4 weeks, 1 day ago (Aug. 3, 2025, 12:36 a.m.)
Issued	27 years ago (Aug. 4, 1998)
Published	27 years ago (Aug. 4, 1998)
Published Online	27 years ago (Aug. 4, 1998)
Published Print	27 years ago (Aug. 4, 1998)

Funders 0

None

BibTeX

@article{Williamson_1998, title={Absence of neurofilaments reduces the selective vulnerability of motor neurons and slows disease caused by a familial amyotrophic lateral sclerosis-linked superoxide dismutase 1 mutant}, volume={95}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.95.16.9631}, DOI={10.1073/pnas.95.16.9631}, number={16}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Williamson, Toni L. and Bruijn, Lucie I. and Zhu, Qinzhang and Anderson, Karen L. and Anderson, Scott D. and Julien, Jean-Pierre and Cleveland, Don W.}, year={1998}, month=aug, pages={9631–9636} }

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