The potential of zwitterionic nanoliposomes against neurotoxic alpha-synuclein aggregates in Parkinson's DiseaseElectronic supplementary information (ESI) available. See DOI: 10.1039/c8nr00632f

The protein α-synuclein (αSN) aggregates to form fibrils in neuronal cells of Parkinson's patients. Here we report on the effect of neutral (zwitterionic) nanoliposomes (NLPs), supplemented with cholesterol (NLP-Chol) and decorated with PEG (NLP-Chol-PEG), on αSN aggregation and neurotoxicity....

Full description

Saved in:
Bibliographic Details
Main Authors: Aliakbari, Farhang, Mohammad-Beigi, Hossein, Rezaei-Ghaleh, Nasrollah, Becker, Stefan, Dehghani Esmatabad, Faezeh, Eslampanah Seyedi, Hadieh Alsadat, Bardania, Hassan, Tayaranian Marvian, Amir, Collingwood, Joanna F, Christiansen, Gunna, Zweckstetter, Markus, Otzen, Daniel E, Morshedi, Dina
Format: Article
Language:
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The protein α-synuclein (αSN) aggregates to form fibrils in neuronal cells of Parkinson's patients. Here we report on the effect of neutral (zwitterionic) nanoliposomes (NLPs), supplemented with cholesterol (NLP-Chol) and decorated with PEG (NLP-Chol-PEG), on αSN aggregation and neurotoxicity. Both NLPs retard αSN fibrillization in a concentration-independent fashion. They do so largely by increasing lag time (formation of fibrillization nuclei) rather than elongation (extension of existing nuclei). Interactions between neutral NLPs and αSN may locate to the N-terminus of the protein. This interaction can even perturb the interaction of αSN with negatively charged NLPs which induces an α-helical structure in αSN. This interaction was found to occur throughout the fibrillization process. Both NLP-Chol and NLP-Chol-PEG were shown to be biocompatible in vitro , and to reduce αSN neurotoxicity and reactive oxygen species (ROS) levels with no influence on intracellular calcium in neuronal cells, emphasizing a prospective role for NLPs in reducing αSN pathogenicity in vivo as well as utility as a vehicle for drug delivery. The mechanism of zwitterionic nanoliposomes to reduce α-synuclein aggregation and neurotoxicity.
ISSN:2040-3364
2040-3372
DOI:10.1039/c8nr00632f