Chrysin-Loaded Chitosan Nanoparticle-Mediated Neuroprotection in Aβ_1-42-Induced Neurodegenerative Conditions in...

Amyloid β plaques and neurofibrillary tangles are the characteristic features of Alzheimer's disease (AD). Plaques of amyloid β play a pivotal role in affecting cognitive functions and memory. Alzheimer's disease is a progressive neurodegenerative disease and is one of the leading causes of dementia worldwide. Several treatment strategies focusing on the amyloid cascade have been implemented to treat AD. The blood-brain barrier (BBB) poses the main obstructive barrier by refraining drugs from penetrating the brain. Nanotechnology is a promising research field for brain drug delivery using nanosized particles. Zebrafish is emerging as a model of interest to elaborate on brain targeting and nanotechnology-based therapeutics for neurodegenerative diseases. In the current study, we have synthesized and characterized chrysin-loaded chitosan nanoparticles (Chr-Chi NPs) and evaluated them for neuroprotection against amyloid-β-induced toxicity. We find that treatment with Chr-Chi NPs helps to retain memory, cognition, and synaptic connections, which are otherwise compromised due to Aβ_1-42 toxicity. The NPs further help in reducing aggregates of amyloid β, thus decreasing neuronal death and generation of reactive oxygen species (ROS). Taken together, our study brings to light a novel strategy for treating AD by a combined action on the neurons and amyloid aggregates mediated by chrysin and chitosan, respectively. Chr-Chi NPs, therefore, have the potential to provide a beneficial combinatorial treatment strategy for AD.