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Multiple Protective Roles of Nanoliposome-Incorporated Baicalein against Alpha-Synuclein Aggregates

Articolo
Data di Pubblicazione:
2021
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.
Tipologia CRIS:
1.1 Articolo in rivista
Keywords:
baicalein; fibrillation; neurotoxicity; Parkinson's disease; zwitterionic nanoliposomes; α-synuclein
Elenco autori:
Aliakbari, F.; Mohammad-Beigi, H.; Abbasi, S.; Rezaei-Ghaleh, N.; Lermyte, F.; Parsafar, S.; Becker, S.; Tafreshi, A. P.; O'Connor, P. B.; Collingwood, J. F.; Christiansen, G.; Sutherland, D. S.; Jensen, P. H.; Morshedi, D.; Otzen, D. E.
Autori di Ateneo:
REZAIE GHALEH NASROLLAH
Link alla scheda completa:
https://iris.unipv.it/handle/11571/1506347
Pubblicato in:
ADVANCED FUNCTIONAL MATERIALS
Journal
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URL

https://onlinelibrary.wiley.com/doi/full/10.1002/adfm.202007765
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