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

Farhang Aliakbari; Hossein Mohammad-Beigi; Nasrollah Rezaei-Ghaleh; Stefan Becker; Faezeh Dehghani Esmatabad; Hadieh Alsadat Eslampanah Seyedi; Hassan Bardania; Amir Tayaranian Marvian; Joanna F Collingwood; Gunna Christiansen; Markus Zweckstetter; Daniel E Otzen; Dina Morshedi

doi:10.1039/c8nr00632f

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

Farhang Aliakbari, Hossein Mohammad-Beigi, Nasrollah Rezaei-Ghaleh, Stefan Becker, Faezeh Dehghani Esmatabad, Hadieh Alsadat Eslampanah Seyedi, Hassan Bardania, Amir Tayaranian Marvian, Joanna F Collingwood, Gunna Christiansen, Markus Zweckstetter, Daniel E Otzen, Dina Morshedi

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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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.

Original language	English
Journal	Nanoscale
Volume	10
Issue	19
Pages (from-to)	9174-9185
Number of pages	12
ISSN	2040-3364
DOIs	https://doi.org/10.1039/c8nr00632f
Publication status	Published - 17 May 2018

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Aliakbari, F., Mohammad-Beigi, H., Rezaei-Ghaleh, N., Becker, S., Dehghani Esmatabad, F., Eslampanah Seyedi, H. A., Bardania, H., Tayaranian Marvian, A., Collingwood, J. F., Christiansen, G., Zweckstetter, M., Otzen, D. E., & Morshedi, D. (2018). The potential of zwitterionic nanoliposomes against neurotoxic alpha-synuclein aggregates in Parkinson's Disease. Nanoscale, 10(19), 9174-9185. https://doi.org/10.1039/c8nr00632f

@article{aa28b28f0b634589be8b89d7a65687ef,

title = "The potential of zwitterionic nanoliposomes against neurotoxic alpha-synuclein aggregates in Parkinson's Disease",

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.",

author = "Farhang Aliakbari and Hossein Mohammad-Beigi and Nasrollah Rezaei-Ghaleh and Stefan Becker and {Dehghani Esmatabad}, Faezeh and {Eslampanah Seyedi}, {Hadieh Alsadat} and Hassan Bardania and {Tayaranian Marvian}, Amir and Collingwood, {Joanna F} and Gunna Christiansen and Markus Zweckstetter and Otzen, {Daniel E} and Dina Morshedi",

year = "2018",

month = may,

day = "17",

doi = "10.1039/c8nr00632f",

language = "English",

volume = "10",

pages = "9174--9185",

journal = "Nanoscale",

issn = "2040-3364",

publisher = "Royal Society of Chemistry",

number = "19",

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Aliakbari, F, Mohammad-Beigi, H, Rezaei-Ghaleh, N, Becker, S, Dehghani Esmatabad, F, Eslampanah Seyedi, HA, Bardania, H, Tayaranian Marvian, A, Collingwood, JF, Christiansen, G, Zweckstetter, M, Otzen, DE & Morshedi, D 2018, 'The potential of zwitterionic nanoliposomes against neurotoxic alpha-synuclein aggregates in Parkinson's Disease', Nanoscale, vol. 10, no. 19, pp. 9174-9185. https://doi.org/10.1039/c8nr00632f

The potential of zwitterionic nanoliposomes against neurotoxic alpha-synuclein aggregates in Parkinson's Disease. / Aliakbari, Farhang; Mohammad-Beigi, Hossein; Rezaei-Ghaleh, Nasrollah et al.
In: Nanoscale, Vol. 10, No. 19, 17.05.2018, p. 9174-9185.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - The potential of zwitterionic nanoliposomes against neurotoxic alpha-synuclein aggregates in Parkinson's Disease

AU - Aliakbari, Farhang

AU - Mohammad-Beigi, Hossein

AU - Rezaei-Ghaleh, Nasrollah

AU - Becker, Stefan

AU - Dehghani Esmatabad, Faezeh

AU - Eslampanah Seyedi, Hadieh Alsadat

AU - Bardania, Hassan

AU - Tayaranian Marvian, Amir

AU - Collingwood, Joanna F

AU - Christiansen, Gunna

AU - Zweckstetter, Markus

AU - Otzen, Daniel E

AU - Morshedi, Dina

PY - 2018/5/17

Y1 - 2018/5/17

N2 - 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.

AB - 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.

U2 - 10.1039/c8nr00632f

DO - 10.1039/c8nr00632f

M3 - Journal article

C2 - 29725687

SN - 2040-3364

VL - 10

SP - 9174

EP - 9185

JO - Nanoscale

JF - Nanoscale

IS - 19

ER -

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

Abstract

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