Usually familial ALS is characterised by the aggregation of mutated SOD1, a protein that normally protects cells from free radical damage. However, the exact composition of these aggregates is not clear. Thus, identifying the other proteins present and if they are modified in any way could help answer how they form and why they are so toxic.

The study, led by Julian Whitelegge, made use of mass spectrometry to uncover the components of these aggregates and to their surprise the researchers discovered that they were composed almost entirely of SOD1.

However, some samples contained trace amounts of random abundant nerve proteins that likely got there by happenstance.

Besides, after analysing ALS mouse spinal cords, it was shown that almost all the SOD1 was fully intact protein and not partial or damaged fragments. Similarly, no evidence was found for extensive chemical modifications (that were not readily removed by DTT treatment).

Though there are many questions still remaining about these aggregates, the study has given provided a starting point, indicating that aggregation is an intrinsic property of mutant SOD1, just like the amyloid plaques associated with Alzheimer’s.

The study appears online in JBC.

Source-ANI
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