Mapping Polypeptide Self-Recognition through ~1H Off-Resonance Relaxation

摘要

Amyloid fibril formation is associated with several neurodegen-erative disorders either through a gain in toxic function or through a loss of function.The prefibrillar soluble oligomers have been shown to be significantly more toxic than the mature amyloid fibrils,as these early aggregates lead to apoptotic or necrotic cell death by causing oxidative stress and altered cellular homeostasis as a result of their interactions with membranes.Solution studies help understand the mechanism of formation of the soluble toxic oligomeric intermediates,and they may provide clues for the inhibition of the early,still reversible,steps in the cascade of events that lead to cell death.