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On August 12, 2022, the team of Professor Shi Shengliang from the Second Affiliated Hospital of Guangxi Medical University and the team of Associate Researcher Yu Yin, Center for Synthetic Biology, Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, cooperated with the team of Associate Researcher Yu Yin, and published the latest results in the Biomaterials journal with: Blood -Research paper on brain barrier Permeable nanoparticles for Alzheimer's disease treatment by selective mitophagy of microglia
In this work, the research team developed a nanoparticle with excellent blood-brain barrier (BBB) permeability composed of Prussian blue/polyamidoamine-type (PAMAM) dendrimer/angiopoietin-2 ( PPA) to restore the physiological function of microglia by regulating mitophagy and scavenging reactive oxygen species (ROS), thereby treating Alzheimer's disease
Alzheimer's disease (AD) is a neurodegenerative disease with an increasing prevalence year by year, and many current drugs that inhibit Aβ (amyloid) fail to effectively improve the symptoms of Alzheimer's
Figure 1.
The research team first prepared and characterized PPA nanomaterials
Figure 2.
The research team used CCK-8 to detect the cell viability of BV-2 cells after PPA treatment, 0.
Figure 3.
To examine the therapeutic effect of PPA nanoparticles on AD, the APP/PS1 double-transgenic Alzheimer's disease mouse model was applied
Figure 4.
PPA was able to rescue the pathological damage and apoptosis of neurons (labeled by NeuN) in AD mice after intravenous injection (Fig.
Figure 5.
Mechanistically, the research team found that PPA effectively triggered mitophagy in microglia in a concentration-dependent manner (Fig.
Figure 6.
To clarify the role of mitophagy in PPA treatment of AD, the autophagy inhibitor 3-MA (3-methyladenine) was used
Figure 7.
In this study, a smart nanoparticle with good biocompatibility and BBB penetration was developed to activate microglial mitophagy and enhance mitochondrial function, thereby significantly reducing ROS and inflammation in AD mice level to achieve memory rescue in AD mice
.
The treatment of Alzheimer's disease by regulating the metabolism of microglia by multifunctional nanoparticles provides a new idea for the treatment of Alzheimer's disease
.
Figure 8.
PPA nanoparticles modulate mitochondrial metabolism to treat Alzheimer's disease
The first author of the article is Zhong Gang, a research assistant in Yu Yin's research group, together with Long Huiping from Shi Shengliang's team; Associate Researcher Yu Yin and Chen Fei, and Professor Shi Shengliang from the Second Affiliated Hospital of Guangxi Medical University are the co-corresponding authors
.
Original source:
Gang Zhong, et al.
Blood-brain barrier Permeable nanoparticles for Alzheimer's disease treatment by selective mitophagy of microglia.
Biomaterials, 12 August 2022, 121690.
