Nayak Vinayak, Patra Sushmita, Rout Shrushti, Jena Atala Bihari, Sharma Rohit, Pattanaik Kali Prasad, Singh Jay, Pandey Shyam S, Singh Ravindra Pratap, Majhi Sanatan, Singh Kshitij Rb, Kerry Rout George
ICAR- National Institute on Foot and Mouth Disease-International Centre for Foot and Mouth Disease, Arugul, Bhubaneswar, Odisha (752050), India.
Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra (410210), India.
Phytomedicine. 2024 Jan;122:155150. doi: 10.1016/j.phymed.2023.155150. Epub 2023 Oct 15.
Alzheimer's disease (AD) is characterized by neuroinflammation linked to amyloid β (Aβ) aggregation and phosphorylated tau (τ) protein in neurofibrillary tangles (NFTs). Key elements in Aβ production and NFT assembly, like γ-secretase and p38 mitogen-activated protein kinase (p38MAPK), contribute to neuroinflammation. In addition, impaired proteosomal and autophagic pathways increase Aβ and τ aggregation, leading to neuronal damage. Conventional neuroinflammation drugs have limitations due to unidirectional therapeutic approaches and challenges in crossing the Blood-Brain Barrier (BBB). Clinical trials for non-steroidal anti-inflammatory drugs (NSAIDs) and other therapeutics remain uncertain. Novel strategies addressing the complex pathogenesis and BBB translocation are needed to effectively tackle AD-related neuroinflammation.
The current scenario demands for a much-sophisticated theranostic measures which could be achieved via customized engineering and designing of novel nanotherapeutics. As, these therapeutics functions as a double edge sword, having the efficiency of unambiguous targeting, multiple drug delivery and ability to cross BBB proficiently.
Inclusion criteria involve selecting recent, English-language studies from the past decade (2013-2023) that explore the regulation of neuroinflammation in neuroinflammation, Alzheimer's disease, amyloid β, tau protein, nanoparticles, autophagy, and phytocompounds. Various study types, including clinical trials, experiments, and reviews, were considered. Exclusion criteria comprised non-relevant publication types, studies unrelated to Alzheimer's disease or phytocompounds, those with methodological flaws, duplicates, and studies with inaccessible data.
In this study, polymeric nanoparticles loaded with specific phytocompounds and coated with an antibody targeting the transferrin receptor (anti-TfR) present on BBB. Thereafter, the engineered nanoparticles with the ability to efficiently traverse the BBB and interact with target molecules within the brain, could induce autophagy, a cellular process crucial for neuronal health, and exhibit potent anti-inflammatory effects. Henceforth, the proposed combination of desired phytocompounds, polymeric nanoparticles, and anti-TfR coating presents a promising approach for targeted drug delivery to the brain, with potential implications in neuroinflammatory conditions such as Alzheimer's disease.
阿尔茨海默病（AD）的特征是神经炎症，其与淀粉样β（Aβ）聚集以及神经原纤维缠结（NFTs）中的磷酸化tau（τ）蛋白相关。Aβ产生和NFT组装中的关键要素，如γ-分泌酶和p38丝裂原活化蛋白激酶（p38MAPK），会导致神经炎症。此外，蛋白酶体和自噬途径受损会增加Aβ和τ的聚集，导致神经元损伤。传统的神经炎症药物由于治疗方法单一以及穿越血脑屏障（BBB）存在挑战而具有局限性。非甾体抗炎药（NSAIDs）和其他疗法的临床试验结果仍不确定。需要新的策略来解决复杂的发病机制和BBB转运问题，以有效应对与AD相关的神经炎症。
当前的情况需要更复杂的治疗诊断措施，这可以通过定制设计新型纳米疗法来实现。因为这些疗法就像一把双刃剑，具有明确的靶向效率、多种药物递送能力以及高效穿越BBB的能力。
纳入标准包括从过去十年（2013 - 2023年）中选择近期的英文研究，这些研究探索神经炎症、阿尔茨海默病、淀粉样β、tau蛋白、纳米颗粒、自噬和植物化合物中神经炎症的调节。考虑了各种研究类型，包括临床试验、实验和综述。排除标准包括不相关的出版物类型、与阿尔茨海默病或植物化合物无关的研究、存在方法学缺陷的研究、重复研究以及数据不可获取的研究。
在本研究中，装载特定植物化合物并涂有靶向BBB上转铁蛋白受体的抗体（抗TfR）的聚合物纳米颗粒。此后，具有有效穿越BBB并与脑内靶分子相互作用能力的工程化纳米颗粒可诱导自噬，这是对神经元健康至关重要的细胞过程，并表现出强大的抗炎作用。因此，所提出的所需植物化合物、聚合物纳米颗粒和抗TfR涂层的组合为向脑内进行靶向药物递送提供了一种有前景的方法，对阿尔茨海默病等神经炎症性疾病具有潜在意义。
