Ontology highlight
ABSTRACT: Background
Lewy body in the substantia nigra is a cardinal pathological feature of Parkinson's disease. Despite enormous efforts, the cause-and-effect relationship between Lewy body formation and the disorder is yet to be explicitly unveiled.Methodology/principal findings
Here, we showed that radiating amyloid fibrils (RAFs) were instantly developed on the surface of synthetic lipid membranes from the ?-sheet free oligomeric species of ?-synuclein through a unit-assembly process. The burgeoning RAFs were successfully matured by feeding them with additional oligomers, which led to concomitant dramatic shrinkage and disintegration of the membranes by pulling off lipid molecules to the extending fibrils. Mitochondria and lysosomes were demonstrated to be disrupted by the oligomeric ?-synuclein via membrane-dependent fibril formation.Conclusion
The physical structure formation of amyloid fibrils, therefore, could be considered as detrimental to the cells by affecting membrane integrity of the intracellular organelles, which might be a molecular cause for the neuronal degeneration observed in Parkinson's disease.
SUBMITTER: Lee JH
PROVIDER: S-EPMC3471876 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
Lee Jung-Ho JH Hong Chul-Suk CS Lee Soonkoo S Yang Jee-Eun JE Park Yong Il YI Lee Daekyun D Hyeon Taeghwan T Jung Seunho S Paik Seung R SR
PloS one 20121015 10
<h4>Background</h4>Lewy body in the substantia nigra is a cardinal pathological feature of Parkinson's disease. Despite enormous efforts, the cause-and-effect relationship between Lewy body formation and the disorder is yet to be explicitly unveiled.<h4>Methodology/principal findings</h4>Here, we showed that radiating amyloid fibrils (RAFs) were instantly developed on the surface of synthetic lipid membranes from the β-sheet free oligomeric species of α-synuclein through a unit-assembly process. ...[more]