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- W2322333302 abstract "Oxidative stress associated cell damage is one of the key factors in neurodegeneration development and is highly related to the presence of transition metal ions including iron. Herein, deferasirox, a high affinity iron chelator, was conjugated to lactoferrin molecules by carbodiimide mediated coupling reaction to create a novel drug delivery system with higher brain permeability through receptor mediated transcytosis. Each lactoferrin molecule was averagely attached to 4 to 6 deferasirox molecules resulting in water-soluble conjugated nanostructures which were purified and characterized. Neuroprotective effects of lactoferrin conjugated nanostructures and their cellular uptake were evaluated in differentiated PC12 cell line, and the molecular mechanisms involved in such neuroprotection were elucidated. Lactoferrin conjugates were able to interfere in apoptotic caspase cascade by affecting the expression level of capsase-3, PARP, Bax and Bcl-2. Furthermore, an elevation in the expression level of autophagy markers including Atg7, Atg12-Atg5 and LC3-II/LC3-I ratio was observed. Intraperitoneal injection of lactoferrin conjugates was able to significantly attenuate learning deficits induced by beta amyloid injection in a rat model of Alzheimer’s disease, which further confirms a potential neuroprotective effect for lactoferrin conjugated deferasirox in neurodegenerative disorder management through metal chelation therapy." @default.
- W2322333302 created "2016-06-24" @default.
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- W2322333302 date "2013-10-28" @default.
- W2322333302 modified "2023-10-16" @default.
- W2322333302 title "Enhanced Brain Delivery of Deferasirox–Lactoferrin Conjugates for Iron Chelation Therapy in Neurodegenerative Disorders: In Vitro and in Vivo Studies" @default.
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- W2322333302 doi "https://doi.org/10.1021/mp4002014" @default.
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