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Amyotrophic lateral sclerosis: Transgenic model and novel neuroprotective agent

Publication ,  Journal Article
Kaddurah-Daouk, R; Matthews, R; Beal, MF
Published in: Neuroscience Research Communications
2000

The discovery of mutations in the human SOD1 gene encoding (Cu, Zn SOD) in patients with familial amyotrophic lateral sclerosis (ALS) has made possible the development of etiological models of the disease. Expression of mutant SOD1 genes in transgenic mice (FALS mice) causes progressive paralytic disease whose general features resemble ALS in humans. Extensive studies strongly suggest that Cu, Zn SOD mutations cause an adverse gain of function that results in enhanced generation of damaging oxygen radicals. Mitochondria are particularly vulnerable to oxidative stress, and mitochondrial swelling and vacuolization are among the earliest pathologic features in the FALS mice harboring the SOD mutations. Mitochondrial dysfunction may lead to ATP depletion, which may contribute to cell death. Creatine buffers against ATP depletion and inhibits the opening of the mitochondrial transition pore, a complex of proteins implicated in apoptosis. We found that oral administration of creatine to FALS mice expressing the G93A mutation produced a dose-dependent improvement in motor performance, extended survival and protected against loss of motor neurons and substantia nigra neurons. Additionally creatine protected against increases in biochemical indices of oxidative damage. The development of the FALS mice enables drug discovery studies in ALS.

Duke Scholars

Published In

Neuroscience Research Communications

DOI

Publication Date

2000

Volume

26

Issue

3

Start / End Page

215 / 226

Related Subject Headings

  • Neurology & Neurosurgery
 

Citation

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MLA
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Kaddurah-Daouk, R., Matthews, R., & Beal, M. F. (2000). Amyotrophic lateral sclerosis: Transgenic model and novel neuroprotective agent. Neuroscience Research Communications, 26(3), 215–226. https://doi.org/10.1002/1520-6769(200005/06)26:3<215::AID-NRC9>3.0.CO;2-Z
Kaddurah-Daouk, R., R. Matthews, and M. F. Beal. “Amyotrophic lateral sclerosis: Transgenic model and novel neuroprotective agent.” Neuroscience Research Communications 26, no. 3 (2000): 215–26. https://doi.org/10.1002/1520-6769(200005/06)26:3<215::AID-NRC9>3.0.CO;2-Z.
Kaddurah-Daouk R, Matthews R, Beal MF. Amyotrophic lateral sclerosis: Transgenic model and novel neuroprotective agent. Neuroscience Research Communications. 2000;26(3):215–26.
Kaddurah-Daouk, R., et al. “Amyotrophic lateral sclerosis: Transgenic model and novel neuroprotective agent.” Neuroscience Research Communications, vol. 26, no. 3, 2000, pp. 215–26. Scival, doi:10.1002/1520-6769(200005/06)26:3<215::AID-NRC9>3.0.CO;2-Z.
Kaddurah-Daouk R, Matthews R, Beal MF. Amyotrophic lateral sclerosis: Transgenic model and novel neuroprotective agent. Neuroscience Research Communications. 2000;26(3):215–226.

Published In

Neuroscience Research Communications

DOI

Publication Date

2000

Volume

26

Issue

3

Start / End Page

215 / 226

Related Subject Headings

  • Neurology & Neurosurgery