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

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. •Phytol and Phytol-PLGANPs impeding the oxidative stress and macromolecular damages induced by Aβ in Neuro-2a cells.•Phytol and Phytol-PLGANPs attenuated Aβ induced proteotoxicity in transgenic Caenorhabditis elegans.•Phytol and Phytol-PLGANPs down regulates AD associated gene expression thereby averting the development of neurotoxic Aβ peptide in both in vitro and in vivo study.•Phytol and Phytol-PLGANPs holds multi-faceted neuroprotective potential against Aβ mediated toxicities.