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The potential of zwitterionic nanoliposomes against neurotoxic alpha-synuclein aggregates in Parkinson's Disease
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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. and Morshedi, Dina (2018) The potential of zwitterionic nanoliposomes against neurotoxic alpha-synuclein aggregates in Parkinson's Disease. Nanoscale, 10 (19). pp. 9174-9185. doi:10.1039/C8NR00632F ISSN 2040-3364.
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Official URL: http://dx.doi.org/10.1039/C8NR00632F
Abstract
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.
Item Type: | Journal Article | ||||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Engineering > Engineering | ||||||||
Journal or Publication Title: | Nanoscale | ||||||||
Publisher: | Royal Society of Chemistry | ||||||||
ISSN: | 2040-3364 | ||||||||
Official Date: | 21 May 2018 | ||||||||
Dates: |
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Volume: | 10 | ||||||||
Number: | 19 | ||||||||
Page Range: | pp. 9174-9185 | ||||||||
DOI: | 10.1039/C8NR00632F | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Restricted or Subscription Access | ||||||||
Date of first compliant deposit: | 9 May 2018 | ||||||||
Date of first compliant Open Access: | 26 May 2019 |
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