Quercetin-Conjugated Superparamagnetic Iron Oxide Nanoparticles Protect AlCl3-Induced Neurotoxicity in a Rat Model of Alzheimer’s Disease via Antioxidant Genes, APP Gene, and miRNA-101

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease with cognitive impairment. Oxidative stress in neurons is considered as a reason for development of AD. Antioxidant agents such as quercetin slow down AD progression, but the usage of this flavonoid has limitations because of its low bioavailability. We hypothesized that quercetin-conjugated superparamagnetic iron oxide nanoparticles (QT-SPIONs) have a better neuroprotective effect on AD than free quercetin and regulates the antioxidant, apoptotic, and APP gene, and miRNA-101. In this study, male Wistar rats were subjected to AlCl3, AlCl3 + QT, AlCl3 + SPION, and AlCl3 + QT-SPION for 42 consecutive days. Behavioral tests and qPCR were used to evaluate the efficiency of treatments. Results of behavioral tests revealed that the intensity of cognitive impairment was decelerated at both the middle and end of the treatment period. The effect of QT-SPIONs on learning and memory deficits were closely similar to the control group. The increase in expression levels of APP gene and the decrease in mir101 led to the development of AD symptoms in rats treated with AlCl3 while these results were reversed in the AlCl3 + QT-SPIONs group. This group showed similar results with the control group. QT-SPION also decreased the expression levels of antioxidant enzymes along with increases in expression levels of anti-apoptotic genes. Accordingly, the antioxidant effect of QT-SPION inhibited progression of cognitive impairment via sustaining the balance of antioxidant enzymes in the hippocampus of AD model rats.

The regulatory roles of microRNAs toward pathogenesis and treatments in Huntington's disease

“…Nanoparticle is a powerful platform able to penetrate BBB to deliver RNA-based treatments into brain regions, and has been developed for more than 10 years. Several types of nanoparticles carrying miRNAs have been examined in different models of neuronal diseases in vivo , including quercetin-conjugated superparamagnetic iron oxide nanoparticles in AD [ 90 ], traceable polymeric nanoparticles in PD [ 91 ], poly(lactic-co-glycolic acid) nanoparticles in stroke [ 92 ], etc. These materials could not only show high capacity and low cytotoxicity to deliver miRNAs into brain regions, but also harbor other biological purposes, such as antioxidant effects and distribution monitoring, showing that nanoparticles with dual or more functions are a trend to develop this type of delivery systems.…”

Phytonanoparticles for the treatment of Alzheimer’s disease: A review

“…Quercetin-nanoparticle (QT-SPIONs) is a better drug to clinically treat the memory loss and associated neurodegenerative disorders. QT-SPIONs in the preclinical study improved the antioxidant function during AD conditions and improved spatial learning memory (Amanzadeh Jajin et al, 2021). It exhibited AChE inhibitory effect and improved the cholinergic transmission.…”

Antioxidant Therapy in Oxidative Stress-Induced Neurodegenerative Diseases: Role of Nanoparticle-Based Drug Delivery Systems in Clinical Translation

“…In a cerebral palsy rabbit model, intravenous treatment of dendrimer-based N-acetyl- l -cysteine (NAC) [ 299 ], a glutathione precursor with antioxidant and anti-inflammatory properties [ 300 ], reduced neuroinflammation and neurological injury, and improved motor function. In general, formulating antioxidants in nanocarriers has enhanced their efficacy due to better stability and/or improved transport to the CNS than free antioxidants [ 301 , 302 , 303 , 304 , 305 , 306 , 307 , 308 , 309 , 310 , 311 , 312 , 313 , 314 , 315 , 316 , 317 , 318 , 319 , 320 , 321 , 322 , 323 , 324 , 325 , 326 , 327 ]. Nanocurcumin has been evaluated as an add-on therapy to Riluzole in a pilot randomized clinical trial for safety and efficacy in ALS [ 272 ] and AD patients as dietary supplements [ 274 ].…”