Journal
PHARMACOLOGICAL RESEARCH
Volume 120, Issue -, Pages 68-87Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2017.03.020
Keywords
Alzheimer's disease; Amyloid-beta; Drug delivery; Nanoparticles; Nerve growth factor; Neuroprotection
Categories
Funding
- FCT - Fundacao para a Ciencia e Tecnologia [PEst-OE/SAU/UI4014]
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Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with amyloid-beta peptide misfolding and aggregation. Neurotrophic factors, such as nerve growth factor (NGF), can prevent neuronal damage and rescue the cholinergic neurons that undergo cell death in AD, reverse deposition of extracellular amyloid plaques and improve cognitive deficits. However, NGF administration is hampered by the poor pharmacokinetic profile of the therapeutic protein and its inability to cross the blood-brain barrier, which requires specialised drug delivery systems (DDS) for efficient NGF delivery to the brain. This review covers the main therapeutic approaches that have been developed for NGF delivery targeting the brain, from polymeric implants to gene and cell-based therapies, focusing on the role of nanoparticulate systems for the sustained release of NGF in the brain as a neuroprotective and disease-modifying approach toward AD. Lipid- and polymer-based delivery systems, magnetic nanoparticles and quantum dots are specifically addressed as promising nanotechnological strategies to overcome the current limitations of NGF-based therapies. (C) 2017 Elsevier Ltd. All rights reserved.
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