Amyloidforming

Amyloidforming refers to the property of certain proteins or peptides to aggregate into amyloid fibrils, which are insoluble, β-sheet–rich structures. The term is used to describe molecules with an intrinsic propensity to form amyloid under physiological conditions or as a result of mutations, environmental stress, or aging.

Aggregation generally proceeds via nucleation-dependent polymerization: a lag phase where misfolded oligomers form, followed by rapid fibril elongation. Misfolded intermediates can be cytotoxic; however, in some biological contexts mature amyloid fibrils serve functional roles, while in others they contribute to disease.

Pathological amyloids include Aβ, tau, α-synuclein, prion protein; systemic amyloidoses involve immunoglobulin light chains (AL), serum amyloid A (AA), transthyretin (ATTR). Functional amyloids include curli fibers produced by many Enterobacteriaceae (CsgA, CsgB) and the melanosome protein Pmel17, which forms amyloid scaffolds that organize pigment deposition.

Detection and research methods used to identify amyloidforming proteins or aggregates include Congo red staining with birefringence, Thioflavin T fluorescence, electron microscopy showing unbranched fibrils, and X-ray diffraction revealing a cross-β pattern.

Impact and context: understanding amyloidforming helps in exploring disease mechanisms, developing inhibitors or antibodies to block aggregation, and appreciating the physiological roles of amyloids in both health and disease.