Amyloid fiber formation

Amyloid is a term used to describe deposits of fibrillar proteins, typically extracellular. The abnormal accumulation of amyloid, amyloidosis, is a term associated with tissue damage caused by amyloid deposition, seen in numerous diseases including neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's. Amyloid deposits consist predominantly of amyloid fibrils, rigid, non-branching structures that form ordered assemblies, characteristically with a cross beta-sheet structure where the sheets run parallel to the direction of the fibril. Often the fibril has a left-handed twist. At least 27 human proteins form amyloid fibrils. Many of these proteins have non-pathological functions; the trigger that leads to abnormal aggregations differs between proteins and is not well understood but in many cases the peptides are abnormal fragments or mutant forms arising from polymorphisms, suggesting that the initial event may be aggregation of misfolded or unfolded peptides. Early studies of Amyloid-beta assembly led to a widely accepted model that assembly was a nucleation-dependent polymerization reaction but it is now understood to be more complex, with multiple 'off-pathway' events leading to a variety of oligomeric structures in addition to fibrils, though it is unclear whether these intermediate steps are required in vivo. An increasing body of evidence suggests that these oligomeric forms are primarily responsible for the neurotoxic effects of Amyloid-beta, alpha-synuclein and tau. Amyloid oligomers are believed to have a common structural motif that is independent of the protein involved and not present in fibrils. Conformation dependent, aggregation specific antibodies suggest that there are 3 general classes of amyloid oligomer structures including annular structures which may be responsible for the widely reported membrane permeabilization effect of amyloid oligomers. Toxicity of amyloid oligomers preceeds the appearance of plaques in mouse models.

Summary from Reactome (R-HSA-977225), read 2026-09-23.