Polymorphismus von Amyloidfibrillen in vivo

Abstract

Polymorphismus ist ein weit verbreitetes Merkmal von in vitro gebildeten Amyloid-artigen Fibrillen, doch blieb bislang unklar,obAmyloidfibrillen in vivo ebenso von diesem Phänomen betroffen sind. Hier zeigen wir,d ass sich verschiedene innerhalb eines Patienten gebildete Amyloidfibrillen erheblich in ihrer Morphologie unterscheiden kçnnen. Wire rhalten diesen Befund mit Amyloidfibrillen aus verschiedenen Organen, bestehend aus nicht-homologen Polypeptidketten sowie aus menschlichem und tierischem Gewebe.Unabhängig von Amyloidtyp und -herkunft finden wir,d ass in vivo gebildete Amyloidfibrillen signifikant polymorphe Eigenschaften aufweisen. Diese Daten lassen darauf schließen, dass die chemischen Grundlagen jener Reaktionen, die in der Selbstorganisation zu Fibrillen zu Polymorphismus führen, in vivo und in vitro grundsätzlichkonserviert sind.

A Substantial Structural Conversion of the Native Monomer Leads to in‐Register Parallel Amyloid Fibril Formation in Light‐Chain Amyloidosis

“…The 6aJL2‐R24G fibrils thus show polymorphism; this was not identifiable from the electron micrographs (Figures C and D). This is in line with the previously reported observation of polymorphism for light‐chain amyloid fibrils in vivo . Sequential resonance assignments were achieved according to previously established protocols .…”

The molecular lifecycle of amyloid – Mechanism of assembly, mesoscopic organisation, polymorphism, suprastructures, and biological consequences

“…Variance in fibril structure, i.e. the polymorphic nature of amyloid fibrils, has been characterised for fibrils formed from synthetic or recombinant monomeric amyloid precursors, as well as those formed in vivo in tissue or by seeding with fibrils from brain tissue of patients with various neurodegenerative diseases [70][71][72]. Amyloid assembly polymorphism resulting from assembly of precursors of identical sequence can be broadly divided into two classes: core polymorphism with differences in the arrangement of monomeric units in the cross-β core, or filament polymorphism with differences in the lateral arrangement of protofilaments in a fibril and the specific contacts they form (Fig.…”

Covalent Tethering and Residues with Bulky Hydrophobic Side Chains Enable Self‐Assembly of Distinct Amyloid Structures

“…Elucidation of the details of amyloid structure and understanding the determinants of their biological activities are therefore of high importance. However, systematic studies of amyloids are convoluted with several obstacles such as molecular‐level polymorphism, conformational heterogeneity, and complex hierarchical organization…”