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

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DOI

  • Farhang Aliakbari, Bioprocess Engineering Research group, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran. morshedi@nigeb.ac.ir.
  • ,
  • 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

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.

OriginalsprogEngelsk
TidsskriftNanoscale
Vol/bind10
Nummer19
Sider (fra-til)9174-9185
Antal sider12
ISSN2040-3364
DOI
StatusUdgivet - 17 maj 2018

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