Multiple Protective Roles of Nanoliposome-Incorporated Baicalein against Alpha-Synuclein Aggregates |
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| Authors: | Farhang Aliakbari Hossein Mohammad-Beigi Shahsanam Abbasi Nasrollah Rezaei-Ghaleh Frederik Lermyte Soha Parsafar Stefan Becker Azita Parvaneh Tafreshi Peter B O'Connor Joanna F Collingwood Gunna Christiansen Duncan S Sutherland Poul Henning Jensen Dina Morshedi Daniel E Otzen |
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| Institution: | 1. Interdisciplinary Nanoscience Centre (iNANO) and Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 14, Aarhus C, DK-8000 Denmark;2. Bioprocess Engineering Department, Institute of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran;3. Department of Neurology, University Medical Center Göttingen, Göttingen, 37075 Germany;4. School of Engineering, University of Warwick, Coventry, CV4 7AL UK;5. Department for NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, 37077 Germany;6. Molecular Medicine Department, Institute of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran;7. Department of Chemistry, University of Warwick, Gibbet Hill, Coventry, CV4 7AL UK;8. Department of Biomedicine, Aarhus University, Aarhus C, 8000 Denmark;9. Interdisciplinary Nanoscience Centre – iNANO-Fysik, iNANO-huset, Aarhus University, Gustav Wieds Vej 14, Aarhus C, DK-8000 Denmark |
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| Abstract: | Nanoparticles are useful for increasing drug stability, solubility, and availability. The small molecule baicalein inhibits fibrillation, and detoxifies aggregates of α-synuclein (αSN) associated with Parkinson's disease (PD), but it suffers from instability, low solubility and consequent low availability. Here it is demonstrated that incorporation of baicalein into zwitterionic nanoliposomes (NLP-Ba) addresses these problems. NLP-Ba inhibits αSN fibril initiation, elongation, secondary nucleation, and also depolymerizes mature fibrils more effectively than free baicalein and prevents soluble αSN aggregates from seeding new fibrils. Importantly, NLP-Ba perturbs oligomers’ capacity to permeabilize the membrane. The interaction between NLP-Ba and αSN is confirmed by different biophysical techniques. This nanosystem crosses the blood-brain barrier in vitro and is effective against rotenone neurotoxicity in vivo. The effect of NLP-Ba on αSN fibrillation/cytotoxicity is attributed to a combination of free baicalein and empty NLPs. The results indicate a neuroprotective role for NLP-Ba in decreasing αSN pathogenicity in PD and highlight the use of nanoliposomes to mobilize poorly soluble hydrophobic drugs. |
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| Keywords: | α-synuclein baicalein fibrillation neurotoxicity Parkinson's disease zwitterionic nanoliposomes |
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