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ALS Aggregates Are Composed Of Only One Protein

Date:
March 31, 2008
Source:
American Society for Biochemistry and Molecular Biology
Summary:
Researchers have provided a big new clue to help combat amyotrophic lateral sclerosis (ALS), deciphering that the dense protein aggregates that contribute to the nerve decay of ALS are composed of just one protein: superoxide dismutase (SOD1). While the aggregation of mutated SOD1, a protein that normally protects cells from free radical damage, is a tell-tale sign of familial ALS, the exact composition of these aggregates has been unclear.

Researchers have provided a big new clue to help combat amyotrophic lateral sclerosis (ALS), deciphering that the dense protein aggregates that contribute to the nerve decay of ALS are composed of just one protein: superoxide dismutase (SOD1).

While the aggregation of mutated SOD1, a protein that normally protects cells from free radical damage, is a tell-tale sign of familial ALS, the exact composition of these aggregates has been unclear. Identifying the other proteins present and if they are modified in some way could help answer how they form and why they are so toxic.

Julian Whitelegge and colleagues Joan S. Valentine and David Borchelt used mass spectrometry to uncover the components of these aggregates and discovered, somewhat surprisingly, that they were composed almost entirely of SOD1 (some samples contained trace amounts of random abundant nerve proteins that likely got there by happenstance).

In addition, their analysis of ALS mouse spinal cords showed almost all the SOD1 was fully intact protein and not partial or damaged fragments. Likewise, the researchers did not find evidence for extensive chemical modifications (that were not readily removed by DTT treatment).

While many questions about these aggregates still remain, this study has given scientists a starting point, suggesting that aggregation is an intrinsic property of mutant SOD1, very much like the amyloid plaques associated with Alzheimer's.

This research was recently published in the Journal of Biological Chemistry.


Story Source:

The above story is based on materials provided by American Society for Biochemistry and Molecular Biology. Note: Materials may be edited for content and length.


Cite This Page:

American Society for Biochemistry and Molecular Biology. "ALS Aggregates Are Composed Of Only One Protein." ScienceDaily. ScienceDaily, 31 March 2008. <www.sciencedaily.com/releases/2008/03/080321140315.htm>.
American Society for Biochemistry and Molecular Biology. (2008, March 31). ALS Aggregates Are Composed Of Only One Protein. ScienceDaily. Retrieved September 30, 2014 from www.sciencedaily.com/releases/2008/03/080321140315.htm
American Society for Biochemistry and Molecular Biology. "ALS Aggregates Are Composed Of Only One Protein." ScienceDaily. www.sciencedaily.com/releases/2008/03/080321140315.htm (accessed September 30, 2014).

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