Work

Amyloid fibril polymorphism: Structural mechanisms of assembly and the links to disease

Year: 2026

Type: review

Abstract: Amyloid fibrils are involved in devastating conditions such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and systemic amyloidosis. They exhibit polymorphism, meaning that a single protein sequence can adopt different amyloid folds that vary with time and self-assembly conditions. Polymorphism confounds structure-based drug design and raises fundamental questions regarding why particular fibril structures form and how they cause disease. Here, we highlight the latest advances in our understanding of amyloid polymorphism, including its structural basis, thermodynamic origins, kinetic influences, and significance for disease. The next frontier will be to predict fibril structures, disentangle the dynamic mechanisms that guide the progression of fibril polymorphs, and illuminate how cofactors and the physiological milieu select for particular polymorphs in disease.

Source: Current Opinion in Structural Biology

DOI: 10.1016/j.sbi.2026.103245

Authors: Alexander I.P. Taylor, Sheena E. Radford

Institution: University of Leeds

Language: English

Topic: Alzheimer's disease research and treatments

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,360