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  The potential of zwitterionic nanoliposomes against neurotoxic alpha-synuclein aggregates in Parkinson's Disease.

Aliakbari, F., Mohammad-Beigi, H., Rezaei-Ghaleh, N., Becker, S., Esmatabad, F. D., Seyedi, H. A. E., et al. (2018). The potential of zwitterionic nanoliposomes against neurotoxic alpha-synuclein aggregates in Parkinson's Disease. Nanoscale, 10(19), 9174-9185. doi:10.1039/C8NR00632F.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0001-44C7-2 Version Permalink: http://hdl.handle.net/21.11116/0000-0002-167F-8
Genre: Journal Article

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 Creators:
Aliakbari, F., Author
Mohammad-Beigi, H., Author
Rezaei-Ghaleh, N., Author
Becker, S.1, Author              
Esmatabad, F. D., Author
Seyedi, H. A. E., Author
Bardania, H., Author
Marvian, A. T., Author
Collingwood, J. F., Author
Christiansen, G., Author
Zweckstetter, M.2, Author              
Otzen, D. E., Author
Morshedi, D., Author
Affiliations:
1Department of NMR Based Structural Biology, MPI for biophysical chemistry, Max Planck Society, ou_578567              
2Research Group of Protein Structure Determination using NMR, MPI for biophysical chemistry, Max Planck Society, ou_578571              

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 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.

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Language(s): eng - English
 Dates: 2018-04-262018-05-21
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1039/C8NR00632F
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Title: Nanoscale
Source Genre: Journal
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Pages: - Volume / Issue: 10 (19) Sequence Number: - Start / End Page: 9174 - 9185 Identifier: -