Amyloid Fibril Components Exhibit Distinct Molecular Recycling Properties

Now, in a paper published in the April 12, 2011, online edition of the Journal of the American Chemical Society investigators at the Institute for Research in Biomedicine (Barcelona, Spain) analyzed the movement of protein fragments within amyloid fibrils.

The investigators used an advanced technique called electrospray ionization mass spectrometry to monitor hydrogen/deuterium exchange in amyloid-beta-fibrils. They found after monitoring recycling for 40 days that both amyloid-beta-40 and amyloid-beta-42 molecules recycled within the fibril population, although to different extents. After 40 days, 80% of the molecules making up amyloid-beta-40 fibrils underwent recycling while only 30% did so in amyloid-beta-42 fibrils. These observations imply that amyloid-beta-42 recycled more slowly, which has implications for understanding the role of amyloid-beta-fibrils in neurotoxicity and for designing therapeutic strategies against Alzheimer's disease.

"In the context of Alzheimer's disease, demonstrating that recycling occurs in the fibrils is a step forward but it is also crucial to identify the recycling species involved; whether they are individual amyloid-beta units or small aggregates made of several units," said senior author Dr. Natalia Carulla, professor of chemistry at the Institute for Research in Biomedicine. "It will be important to address if differences in the recycling species within amyloid-beta-40 and amyloid-beta-42 fibrils are relevant in the development of Alzheimer's disease. We are now working towards this aim. Once we have this information, we will be in a position to devise new therapeutic strategies that can modulate recycling."

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