Conquer the dawn of Alzheimer's disease!

Alzheimer's disease (AD), commonly known as Alzheimer's, is a neurodegenerative disease, a mitochondrial dysfunction closely related to amyloid fibrils (Aβ) deposition and neurofibrillary tangles (NFTs)
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Drugs for the treatment of AD have been developed, but the effects are very limited.
The main reasons are: poor impact on cognitive function or significant side effects and weak blood-brain barrier penetration, which makes it difficult to achieve the desired therapeutic effect
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In previous studies, it was found that oxidative stress is a common physiological variation in early AD neurons, and it is closely related to the formation of Aβ and NFTs
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Simply put, Aβ and intracellular reactive oxygen species are in a synergistic and incremental relationship, which can further increase the intracellular reactive oxygen species ROS production, change the mitochondrial membrane potential, and destroy the Ca2+ homeostasis.
NFTs can cause mitochondrial dysfunction
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These two pathological factors interact in a positive feedback manner, eventually leading to endogenous neuronal apoptosis, leading to the occurrence of Alzheimer's disease
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In addition, intracellular reactive oxygen species ROS can also induce neuroinflammation.
Therefore, intracellular reactive oxygen species ROS are considered to be a key factor in the early stage of AD
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Based on the above, we know that eliminating ROS in cells can prevent neurodegenerative mutations, that is, alleviate the symptoms of Alzheimer's disease
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In October 2021, a research team from Jinan University published a paper "A Functionalized Octahedral Palladium Nanozyme as a Radical Scavenger for Ameliorating Alzheimer's Disease" in "ACS APPLIED MATERIALS&INTERFACES"
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In this study, the researchers designed and prepared the octahedral palladium (Pd) nanoenzyme composite material (Pd@PEG@ Bor), and the traditional Chinese medicine component Borneol (Bor) was coupled to the surface of the Pd@PEG nanomaterial.
Improve the efficiency of crossing the blood-brain barrier and targeting neurons
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Legend: Schematic diagram of the experimental principle of composite materials used to treat AD mice.
Researchers have characterized the biology of composite materials from the aspects of anti-oxidation, biocompatibility, elimination of ROS, blood-brain barrier penetration experiments, and mouse behavior.
The scientific performance proves that this composite material can improve the efficiency of crossing the blood-brain barrier and target neurons, eliminate excessive ROS in cells, maintain mitochondrial membrane potential and calcium ion levels, inhibit the production and aggregation of Aβ, and reduce nerves Inflammation, protect neurons, and further improve the cognitive impairment of AD mice, can effectively alleviate the symptoms of AD
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(1) Antioxidant activity test
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The experimental results show that: individual Pd nanoparticles (Pd NPs) and composite materials (Pd@PEG@Bor) have strong scavenging ability to hydroxyl radicals and singlet reactive oxygen species, and the higher the concentration, the stronger the scavenging ability
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The modification of Pd NPs by borneol (BOR) and PEG does not affect the antioxidant capacity.
Therefore, the function of composite materials can be improved by modifying functional groups, which is also one of the basic principles of this research
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Legend: The ability of Pd NPs and Pd@PEG@Bor to eliminate ROS
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(A) Containing ·OH, Pd NPs (20 μg/mL) and Pd@PEG@Bor (20 μg/mL); (B) Pd@PEG@Bor samples with different concentrations and ·OH; (C) Containing 1O2 and Pd NPs (20 μg/mL) samples and Pd@PEG@Bor (20μg/mL); (D) Pd@PEG@Bor samples containing 1O2 and different concentrations; (2) Biocompatibility experiments
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The good biocompatibility of nanomaterials is a prerequisite for clinical application
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Experimental data shows that: Pd@PEG@Bor is not harmful to normal biofilms
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Using the CCK-8 method, after 24 hours of treatment of the cells with the composite material, the cell viability continued to be greater than 90%.
After 72 hours of treatment, most of the cells were still alive and showed good biocompatibility
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More importantly, the researchers found no damage to the brain (thalamus, hippocampus, and cortex) and major organs (heart, liver, spleen, lung, and kidney) of the mice after 24 hours of injection with the composite tail vein
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In short, in vitro and in vivo experiments show that the composite material has good biocompatibility and weak cytotoxicity
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Legend: Pd NPs and Pd@PEG@Bor biocompatibility experiment
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(A) Uptake of RBT, Pd@RBT and Pd@PEG@Bor@ RBT by SH-SY5Y cells (scale bar = 20 μm)
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(B) SH-SY5Y cells were treated with Pd@PEG@Bor@RBT at different concentrations (5, 10, 20, 40 μg/mL) after 24 hours
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(C) Images and quantitative results of the rupture activity of erythrocyte membrane in mice treated with different concentrations of Pd@PEG@Bor
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(D) 24 h cytotoxicity of Pd@PEG@Bor to SH-SY5Y cells and bEnd3 cells
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(3) Pd@PEG@Bor eliminates reactive oxygen species and decreases Aβ content in vitro
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In the study, the researchers used staining to indicate the content of reactive oxygen species with fluorescence intensity, and used ThT staining to detect Aβ aggregates
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In the experiment, after adding hydrogen peroxide to the blank sample, the reactive oxygen species of the cells increased significantly.
After adding Pd@PEG or Pd@PEG@Bor, the reactive oxygen species of the cells decreased significantly, indicating that they are excellent ROS scavengers
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After adding Pd@PEG and Pd@PEG@Bor for 24 h, the fluorescence intensity of ThT of the cells decreased significantly, indicating that Pd@PEG and Pd@PEG@Bor can reduce the production and deposition of Aβ by alleviating oxidative stress
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Legend: Pd@PEG@Bor eliminates reactive oxygen species and reduces Aβ content in vitro (4) The ability of Pd@PEG@Bor to cross the blood-brain barrier in vitro and in vivo
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The researchers used RBT as a probe to compare the distribution of Pd NPs and Pd@PEG@Bor in the mouse parietal cortex and hippocampus using a confocal laser microscope
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It was found that the fluorescence intensity in the parietal cortex and hippocampus of the mice treated with Pd@PEG@Bor was high and mainly concentrated in the cytoplasm
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The penetration rate of Pd@PEG@Bor is 5.
5 times that of Pd NPs
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In short, this experiment confirms that Bor can promote the effective penetration of the blood-brain barrier
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Legend: Pd@PEG@Bor's ability to cross the blood-brain barrier in vitro and in vivo
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(A) Schematic diagram of the blood-brain barrier model
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(B) In vitro blood-brain barrier permeability of Pd NPs and Pd@PEG@Bor
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(C) Distribution of Pd@RBT and Pd@PEG@Bor@RBT in the cerebral cortex of normal mice (D) Distribution of Pd@RBT and Pd@PEG@Bor@RBT in the hippocampus of normal mice (5) AD small Rat behavior experiment
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AD mice showed obvious anxiety and depression behaviors in the experiment
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However, after intravenous injection of Pd@PEG@Bor, anxiety and depression behavior improved
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In other behavioral experiments, it was proved that Pd@PEG@Bor treatment can improve the research ability and memory ability of AD mice
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In conclusion, behavioral experiments in mice show that composite materials can effectively alleviate cognitive deficits in AD mice
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 Summary: Researchers have synthesized a new type of nanocomposite material Pd@PEG@Bor, which can be used to improve Alzheimer’s disease, reduce Aβ levels, improve neuroinflammation, improve learning and memory, and find a way to overcome this difficult disease.
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End Reference: [1]https://doi.
org/10.
1021/acsami.
1c06687