Abstract
BackgroundLewy 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 FindingsHere, 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. 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 α-synuclein via membrane-dependent fibril formation.ConclusionThe 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.
Highlights
Amyloidogenesis, insoluble protein nanofibril formation from innocuous soluble proteins, is the common phenomenon found in various neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Prion diseases actual mechanisms of the cell death in relation to amyloidogenesis remain largely unknown [1,2,3]
The physical structure formation of amyloid fibrils, 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
Remarkable development of radiating amyloid fibrils (RAFs) from the surface of lipid membranes was observed as the asynuclein oligomers were incubated with the liposomes made of phosphatidylcholine (PC) for less than 5 min in 20 mM Mes, pH 6.5, under quiescent condition at room temperature (Figure 1A)
Summary
Amyloidogenesis, insoluble protein nanofibril formation from innocuous soluble proteins, is the common phenomenon found in various neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Prion diseases actual mechanisms of the cell death in relation to amyloidogenesis remain largely unknown [1,2,3]. Instead of the prevailing pursuit of chemical and biological causes for cytotoxicity, physical and mechanical effects of amyloidogenesis directly responsible for the cellular degeneration have been investigated in this study to unveil molecular etiology of the neurodegenerative disorders. Despite the complexity of intricate cellular activities, cells are well-organized through functional compartmentalization. Potential toxic substances such as diverse hydrolytic enzymes and biomolecules involved in redox reactions are sequestered within membrane-enclosed organelles such as lysosomes and mitochondria. Their latent toxic activities contained within the membrane structures are coordinated to achieve normal cellular biogenesis. The cause-and-effect relationship between Lewy body formation and the disorder is yet to be explicitly unveiled
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
