Unveiling the Three-Dimensional Organization of Atrial Natriuretic Peptide Amyloid Fibrils

The project aims to elucidate the 3D organization of atrial natriuretic peptide (ANP) amyloids. These fibrils responsible for the onset of Isolated Atrial Amyloidosis (IAA), a localized form of cardiac amyloidosis primarily affecting the heart atria. IAA is characterized by the deposition of insoluble amyloid fibrils in the atrial tissue of ANP, a hormone synthesized by the atria. ANP fibrils lead to the disruption of tissue architecture and electrical conduction. Structural information on the architecture of ANP fibrils is lacking, hindering a deep understanding of their interaction with the environment and the mechanisms leading to the formation of the fibrillar structures. Advancements in helical reconstruction procedures in cryo-EM and in extraction techniques of ex-vivo amyloid fibrils offer opportunities to explore the structural characteristics of amyloids. This research could pave the way for targeted therapeutic interventions and improved diagnostic strategies for IAA.