Amyloid Oligomer Structures and Toxicity

摘要

Amyloid accumulation is commonly associated with a number of important human degenerative diseases andrecent findings indicate that soluble amyloid oligomers may represent the primary pathological species in degenerativediseases. Amyloid oligomers are structurally and morphologically diverse, raising the question on whether this diversity ispathologically significant and whether different types of oligomers may have different toxic activities. Many of theamyloids associated with neurodegenerative diseases form three immunologically distinct types of oligomers. Fibrillaroligomers are structurally related to fibrils and may represent small pieces of fibrils or fibril protofilaments. Prefibrillaroligomers are kinetic intermediates in fibril formation and annular protofibrils that resemble membrane pores. These threeclasses of oligomers share common structures and toxic activities. Focus on these common mechanisms of toxicityprovides a means of simplifying the list of primary disease mechanisms and opens the possibility of developing broadspectrum therapeutics that target several amyloid related degenerative diseases.