Regulation of neuroinflammation in Alzheimer's disease via nanoparticle-loaded phytocompounds with anti-inflammatory and autophagy-inducing properties

Abstract

Background: 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.

Purpose: 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.

Methods: 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.

Results: 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.

Keywords: Amyloid β; Autophagy; Nanotherapeutics; Neurofibrillary tangles; Neuroinflammation; Phytocompounds; Tau protein.