Transmissible amyloid

Abstract

There are around 30 human diseases associated with protein misfolding and amyloid formation, each one caused by a certain protein or peptide. Many of these diseases are lethal and together they pose an enormous burden to society. The prion protein has attracted particular interest as being shown to be the pathogenic agent in transmissible diseases such as kuru, Creutzfeldt–Jakob disease and bovine spongiform encephalopathy. Whether similar transmission could occur also in other amyloidoses such as Alzheimer's disease, Parkinson's disease and serum amyloid A amyloidosis is a matter of intense research and debate. Furthermore, it has been suggested that novel biomaterials such as artificial spider silk are potentially amyloidogenic. Here, we provide a brief introduction to amyloid, prions and other proteins involved in amyloid disease and review recent evidence for their potential transmission. We discuss the similarities and differences between amyloid and silk, as well as the potential hazards associated with protein‐based biomaterials.

Amyloid fibril polymorphism: a challenge for molecular imaging and therapy

“…The notion of seeded nucleation reminiscent of prion transmission has been intensively discussed in the literature over the past years and includes fibrils of Ab, Tau, a-syn, PrP, SAA and others [2,[55][56][57]. As one example let us consider Ab.…”

Silk Spinning in Silkworms and Spiders

“…However, the former transition is a bimolecular event that results in a defined soluble and globular structure, while the latter transition involves multiple intermolecular interactions and results in insoluble fibrils. The SpCT was recently found (using a web-based tool for prediction of amyloidogenic regions in proteins, waltz-switchlab.org) [47] to contain three amyloidogenic regions (Figure S1) [48], which can also be found using the Tango tool [49,50,51]. Analogous regions can be found in FibNT (Figure S1), further pointing to the possibility that FibNT and SpCT have similar functions in the control of fiber formation.…”

Differential recruitment efficacy of patient-derived amyloidogenic and myeloma light chain proteins by synthetic fibrils—A metric for predicting amyloid propensity

“…Thus, de novo fibrillogenesis from soluble VL domains can be rapid and requires misfolding of the VL, allowing structured self-association into thermodynamically stable multimers that act as templates, or seeds, for the recruitment of additional VL domains. Template-mediated seeding is a universal paradigm in amyloid-related pathologies that underlies the proposed transmissibility of amyloid diseases [46–50]. …”