1. Phytol loaded PLGA nanoparticles regulate the expression of Alzheimer's related genes and neuronal apoptosis against amyloid-β induced toxicity in Neuro-2a cells and transgenic Caenorhabditis elegans.
- Author
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Sathya S, Shanmuganathan B, Balasubramaniam B, Balamurugan K, and Devi KP
- Subjects
- Amyloid Precursor Protein Secretases metabolism, Amyloid beta-Peptides metabolism, Amyloid beta-Peptides toxicity, Animals, Caenorhabditis elegans drug effects, Caenorhabditis elegans genetics, Caspase 3 metabolism, Cell Line, Tumor, Cholinesterase Inhibitors pharmacology, Drug Carriers chemistry, Membrane Potential, Mitochondrial drug effects, Mice, Mice, Inbred BALB C, Mice, Transgenic, Neurons drug effects, Oxidative Stress drug effects, Peptide Fragments toxicity, Apoptosis drug effects, Gene Expression drug effects, Nanoparticles chemistry, Neuroprotective Agents pharmacology, Phytol pharmacology, Polylactic Acid-Polyglycolic Acid Copolymer chemistry
- Abstract
Amyloid β (Aβ) induced neurotoxicity has been postulated to initiate synaptic loss and subsequent neuronal degeneration in Alzheimer's disease (AD). The nanoparticles based drug carrier system is considered as a promising therapeutic strategy to combat this incurable disease. It was also found to inhibit cholinesterase activity and apoptosis mediated cell death in Neuro-2a cells. The in vivo study further revealed that the Phytol and Phytol-PLGA NPs (Poly Lactic-co-Glycolic Acid Nanoparticles) was found to increase the lifespan, chemotaxis behavior and decrease Aβ deposition & ROS (Reactive oxygen species) production in transgenic Caenorhabditis elegans models of AD (CL2006, CL4176). Phytol and Phytol-PLGA NPs treatment downregulated the expression of AD associated genes viz Aβ, ace-1 and hsp-4 and upregulated the gene involved in the longevity to nematodes (dnj-14) and it also reduced the expression of Aβ peptide at the protein level. Our results of in vitro and in vivo studies suggest that Phytol and Phytol-PLGA NPs hold promising neuroprotective efficacy and targets multiple neurotoxic mechanisms involved in the AD progression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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