Neuroscience Lab, Centre for Molecular and Nanomedical Science, Centre for Nanoscience and Nanotechnology, School of Bio and Chemical Engineering, Sathyabama Institute of Science and Technology (Deemed to be University), Jeppiaar Nagar, Rajiv Gandhi Salai, Chennai 600119, Tamil Nadu, India.
JIS Institute of Advanced Studies and Research, JIS University, Kolkata 700091, West Bengal, India.
ACS Chem Neurosci. 2022 Jul 6;13(13):2017-2034. doi: 10.1021/acschemneuro.2c00240. Epub 2022 Jun 13.
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 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.
淀粉样β斑块和神经原纤维缠结是阿尔茨海默病（AD）的特征性病变。淀粉样β斑块在影响认知功能和记忆方面起着关键作用。阿尔茨海默病是一种进行性神经退行性疾病，是全球痴呆症的主要病因之一。目前已经实施了几种针对淀粉样蛋白级联反应的治疗策略来治疗 AD。血脑屏障（BBB）通过阻止药物穿透大脑，构成了主要的阻塞性障碍。纳米技术是一种很有前途的脑内药物递送研究领域，它使用纳米级颗粒。斑马鱼作为一种新兴的模式生物，在研究脑靶向和基于纳米技术的神经退行性疾病治疗方面引起了人们的关注。在本研究中，我们合成并表征了负载白杨素的壳聚糖纳米粒子（Chr-Chi NPs），并评估了它们对淀粉样β诱导的毒性的神经保护作用。我们发现，Chr-Chi NPs 的治疗有助于保留记忆、认知和突触连接，否则这些功能会因 Aβ毒性而受损。这些纳米粒子进一步有助于减少淀粉样β的聚集，从而减少神经元死亡和活性氧（ROS）的产生。总之，我们的研究揭示了一种通过白杨素和壳聚糖分别作用于神经元和淀粉样蛋白聚集体来治疗 AD 的新策略。因此，Chr-Chi NPs 有可能为 AD 提供一种有益的联合治疗策略。
