ABSTRACT
Alzheimer's disease perpetually demands enormous research on the development of effective treatment strategies. The present study aims to define the role of Oxyresveratrol (OXY) alone and in combination with Alkoxy glycerols (AKG) to reduce Tau protein level and improve the climbing behaviour of Drosophila fly models expressed with human-Tau protein. Oxyresveratrol, a polyphenolic stilbene, possesses a wide range of biological activities like antioxidant, anti-inflammatory, and neuroprotective effects. Nevertheless, chemical instability and low solubility of OXY in aqueous solutions reduce its bioavailability and hinder it from exerting neuroprotective activities. An inclusion complex of OXY with ß- cyclodextrin (CD) (OXY-CD complex) was employed in the study for increased dissolution rate and oral availability of OXY. Fish oils and their derivatives have a plethora of applications in in vivo biological activities. Herein, we also remark on the role of AKG in reducing Tau protein level in flies by enhancing OXY-CD activity. Dietary supplementation of OXY-CD together with AKG improved the learning and memory abilities during the climbing assay in Tau flies. The study highlights OXY-CD and AKG as neuroprotective agents and put forward a plausible approach towards the increased permeability of pharmacological agents across the blood-brain barrier (BBB) for the central nervous system elicited by AKG.
Subject(s)
Alzheimer Disease/pathology , Glycerol/pharmacology , Neuroprotective Agents/pharmacology , Plant Extracts/pharmacology , Stilbenes/pharmacology , tau Proteins/drug effects , Animals , Animals, Genetically Modified , Behavior, Animal/drug effects , Benzofurans/pharmacology , Drosophila melanogaster , Humans , Learning/drug effects , Memory/drug effectsABSTRACT
The concept of exosomes has been progressively changed from the status of cellular trashcans to multitasking organelles involved in many processes, including internalization, transport and transfer of macromolecules such as proteins, lipids and nucleic acids. While underpinning the mechanisms behind neurodegeneration and neuronal loss, exosomes were shown to be involved in carrying pathological misfolded proteins, propagation of ß-amyloid protein and hyper-phosphorylated tau proteins across the brain that ultimately leads to the onset of Alzheimer's disease (AD), the most prevailing multifactorial neurodegenerative disorder. A potential novel therapeutic role of exosomes in AD intervention is suggested by their ability to increase Aß clearance. This review aims to highlight the important pathological mechanisms as well as therapeutic strategies involving exosomes towards AD prevention.
