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Issue 19, 2018
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The potential of zwitterionic nanoliposomes against neurotoxic alpha-synuclein aggregates in Parkinson's Disease

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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.

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

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Publication details

The article was received on 23 Jan 2018, accepted on 17 Apr 2018 and first published on 26 Apr 2018


Article type: Paper
DOI: 10.1039/C8NR00632F
Citation: Nanoscale, 2018,10, 9174-9185
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    The potential of zwitterionic nanoliposomes against neurotoxic alpha-synuclein aggregates in Parkinson's Disease

    F. Aliakbari, H. Mohammad-Beigi, N. Rezaei-Ghaleh, S. Becker, F. Dehghani Esmatabad, H. A. Eslampanah Seyedi, H. Bardania, A. Tayaranian Marvian, J. F. Collingwood, G. Christiansen, M. Zweckstetter, D. E. Otzen and D. Morshedi, Nanoscale, 2018, 10, 9174
    DOI: 10.1039/C8NR00632F

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