The BRICHOS Domain

Abstract

Prepared by leading experts, the series contains diverse types of contributions, from snapshot volumes that allow fast entry to a general topic to those covering more specialized aspects in the field of protein folding and structure. In common, these Briefs aim at covering essential concepts, methodologies and ideas in the context of contemporary research in protein science. Through these compact volumes, this series serves as a venue for publication between typical research papers, review articles and full books, and aims at a broad audience, from students to researchers in academia and industry.

Amyloid inhibition by molecular chaperones in vitro can be translated to Alzheimer's pathology in vivo

“…1,4,14 The BRICHOS domain is found in 13 different families and associated to different diseases. 3,48,49 Amyloidogenic peptides can be released from proproteins in which the suggested primary function of BRICHOS is to prevent the potentially amyloid-forming polypeptides from aggregation. 49 The two most studied examples are Bri2 BRICHOS, which is found in dementia-associated integral membrane protein 2B (ITM2B aka Bri2) and BRICHOS from prosurfactant protein C (proSP-C), which is implicated in interstitial lung disease.…”

“…3,48,49 Amyloidogenic peptides can be released from proproteins in which the suggested primary function of BRICHOS is to prevent the potentially amyloid-forming polypeptides from aggregation. 49 The two most studied examples are Bri2 BRICHOS, which is found in dementia-associated integral membrane protein 2B (ITM2B aka Bri2) and BRICHOS from prosurfactant protein C (proSP-C), which is implicated in interstitial lung disease. 48–50 proSP-C BRICHOS exists predominately as a trimer and inhibits Aβ42 fibrillization by binding to the fibril surface and preventing secondary nucleation events.…”

“…49 The two most studied examples are Bri2 BRICHOS, which is found in dementia-associated integral membrane protein 2B (ITM2B aka Bri2) and BRICHOS from prosurfactant protein C (proSP-C), which is implicated in interstitial lung disease. 48–50 proSP-C BRICHOS exists predominately as a trimer and inhibits Aβ42 fibrillization by binding to the fibril surface and preventing secondary nucleation events. 4 Studies using a single-point mutant of proSP-C BRICHOS, which favors the monomeric state, showed that also this variant predominately inhibits secondary nucleation and captures the smallest secondary nucleation-competent Aβ oligomers.…”