TY - JOUR
T1 - Common Fibril Structures Imply Systemically Conserved Protein Misfolding Pathways In Vivo
AU - Annamalai, Karthikeyan
AU - Liberta, Falk
AU - Vielberg, Marie Theres
AU - Close, William
AU - Lilie, Hauke
AU - Gührs, Karl Heinz
AU - Schierhorn, Angelika
AU - Koehler, Rolf
AU - Schmidt, Andreas
AU - Haupt, Christian
AU - Hegenbart, Ute
AU - Schönland, Stefan
AU - Schmidt, Matthias
AU - Groll, Michael
AU - Fändrich, Marcus
N1 - Publisher Copyright:
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2017/6/19
Y1 - 2017/6/19
N2 - Systemic amyloidosis is caused by the misfolding of a circulating amyloid precursor protein and the deposition of amyloid fibrils in multiple organs. Chemical and biophysical analysis of amyloid fibrils from human AL and murine AA amyloidosis reveal the same fibril morphologies in different tissues or organs of one patient or diseased animal. The observed structural similarities concerned the fibril morphology, the fibril protein primary and secondary structures, the presence of post-translational modifications and, in case of the AL fibrils, the partially folded characteristics of the polypeptide chain within the fibril. Our data imply for both analyzed forms of amyloidosis that the pathways of protein misfolding are systemically conserved; that is, they follow the same rules irrespective of where inside one body fibrils are formed or accumulated.
AB - Systemic amyloidosis is caused by the misfolding of a circulating amyloid precursor protein and the deposition of amyloid fibrils in multiple organs. Chemical and biophysical analysis of amyloid fibrils from human AL and murine AA amyloidosis reveal the same fibril morphologies in different tissues or organs of one patient or diseased animal. The observed structural similarities concerned the fibril morphology, the fibril protein primary and secondary structures, the presence of post-translational modifications and, in case of the AL fibrils, the partially folded characteristics of the polypeptide chain within the fibril. Our data imply for both analyzed forms of amyloidosis that the pathways of protein misfolding are systemically conserved; that is, they follow the same rules irrespective of where inside one body fibrils are formed or accumulated.
KW - Alzheimer's disease
KW - Parkinson's disease
KW - conformational disease
KW - prions
KW - protein aggregation
UR - http://www.scopus.com/inward/record.url?scp=85019610260&partnerID=8YFLogxK
U2 - 10.1002/anie.201701761
DO - 10.1002/anie.201701761
M3 - Article
C2 - 28544119
AN - SCOPUS:85019610260
SN - 1433-7851
VL - 56
SP - 7510
EP - 7514
JO - Angewandte Chemie International Edition in English
JF - Angewandte Chemie International Edition in English
IS - 26
ER -
