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Tracing a killer's path in Lou Gehrig's disease

hinting that, for a reason they do not yet understand, spinal cord neurons are particular targets of the mutant protein.

Such aggregation of the mutant protein with Bcl-2 could trigger the cell death machinery by either depleting Bcl-2 or even converting it into a cell death activator, concluded the researchers.

The preferential aggregation of mutant SOD1 in spinal cord mitochondria "defines a potential Achilles' heel that may render spinal cord cells susceptible to this mutant protein," wrote the researchers.

Jian Liu, Concepcin Lillo, P. Andreas Jonsson, Christine Vande Velde, Christopher M. Ward, Timothy M. Miller, Jamuna R. Subramaniam, Jeffery D. Rothstein, Stefan Marklund, Peter M. Andersen, Thomas Brnnstrm, Ole Gredal, Philip C. Wong, David S. Williams, and Don W. Cleveland: "Toxicity of Familial ALS-Linked SOD1 Mutants from Selective Recruitment to Spinal Mitochondria"

Piera Pasinelli, Mary Elizabeth Belford, Niall Lennon, Brian J. Bacskai, Bradley T. Hyman, Davide Trotti, and Robert H. Brown, Jr.: "Amyotrophic Lateral Sclerosis-Associated Mutant Proteins Bind and Aggregate with Bcl-2 in Spinal Cord Mitochondria"


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Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
7-Jul-2004


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