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Innovation: Zhang Yunlong's group at the School of Basic Medical Sciences, Guangzhou Medical University, Li Shiying's group at the School of Pharmacy, and Xu Pingyi's group at the First Affiliated Hospital cooperate to build a "Trojan horse" drug delivery system across the blood-brain barrier, targeting dopamine neurons to deliver new types of antibodies Parkinson's disease drugs.
Keywords: Parkinson's disease, 4,4'-dimethoxychalcone, neuroprotective effect, Guangzhou Medical University Parkinson's disease (Parkinson's disease, PD) is a common neurodegenerative disease, its pathological feature is midbrain substantia nigra dopamine Dopamine (DA) neuronal degeneration, and the Lewy bodies with α-synuclein deposition as the main component in the remaining neurons.
The pathogenesis may be related to mitochondrial dysfunction, autophagy-lysosomal system disorders, and neuroinflammation.
There is still a lack of effective drug treatments.
The search for new and effective drugs and mechanisms has important clinical significance for intervention in DA neuronal degeneration.
Recently, Zhang Yunlong's research group from the School of Basic Medical Sciences of Guangzhou Medical University, in conjunction with the Li Shiying's research group of the School of Pharmacy and Xu Pingyi's research group of the First Affiliated Hospital, designed and synthesized a "Trojan horse" drug delivery system (RVG-nDMC) that crosses the blood-brain barrier.
For the targeted delivery of flavonoids-4,4'-dimethoxychalcone (DMC) to dopamine neurons in the substantia nigra of the midbrain.
Studies have shown that RVG-nDMC can efficiently penetrate the blood-brain barrier and be taken up by DA neurons, and improve the motor deficit and DA neuron death in PD model mice.
The study combined RNA-sequencing, metabolomics and electron microscopy, and found that RVG-nDMC can inhibit the ubiquitination and degradation of the PD model dopamine synthesis rate-limiting enzyme—tyrosine hydroxylase (TH), and promote black DA neurons Synthesize dopamine and reduce the oxidative stress damage of DA neurons caused by ubiquitinated TH.
In addition, RVG-nDMC can also be taken up by substantia nigra microglia, and reduce the damage of neuroinflammation to DA neurons through anti-inflammatory effects.
RVG-nDMC showed no toxic and side effects on various organ systems.
This study reveals the new neuropharmacological mechanism of DMC against PD, and also provides a new idea for the treatment and intervention of PD.
Related results were published in Advanced Science.
Zhang Yunlong of the School of Basic Medical Sciences, Li Shiying of the School of Pharmacy, and Xu Pingyi of the First Affiliated Hospital are the corresponding authors of the paper.
Doctoral student Zhang Wenlong, experimentalist Chen Huaqing, master students Ding Liuyan and Gong Junwei are the co-first authors of the paper.
The research was supported by the National Natural Science Foundation of China, the National Key R&D Program, the Guangzhou Science and Technology Plan Project, and the Guangzhou Medical University Research Startup Fund.
WILEY paper information: Trojan Horse Delivery of 4,4′-Dimethoxychalcone for Parkinsonian NeuroprotectionWenlong Zhang, Huaqing Chen, Liuyan Ding,Junwei Gong, Mengran Zhang, Wenyuan Guo,Pingyi Xu, Shiying Li, Yunlong ZhangAdvanced ScienceDOI: 10.
1002/advs.
202004555 click "Read the original text" in the lower left corner to view the original text of the paper.
Introduction to AdvancedScience Journal "Advanced Science" (Advanced Science) Wiley is a high-quality open source journal founded in 2014.
It publishes innovative achievements and cutting-edge progress in various fields such as materials science, physical chemistry, biomedicine, and engineering.
The journal is dedicated to disseminating scientific research results to the public to the greatest extent, and all articles are freely available.
The latest impact factor is 15.
840, and the 2020 SCI journals of the Chinese Academy of Sciences will be divided into the Q1 area of the material science category and the Q1 area of the engineering technology category. Press and hold the QR code on the official WeChat platform of AdvancedScienceNewsWiley's scientific research information.
Follow us to share cutting-edge information|Focus on scientific research trends to publish scientific research news or apply for information sharing, please contact: ASNChina@Wiley.
com
Keywords: Parkinson's disease, 4,4'-dimethoxychalcone, neuroprotective effect, Guangzhou Medical University Parkinson's disease (Parkinson's disease, PD) is a common neurodegenerative disease, its pathological feature is midbrain substantia nigra dopamine Dopamine (DA) neuronal degeneration, and the Lewy bodies with α-synuclein deposition as the main component in the remaining neurons.
The pathogenesis may be related to mitochondrial dysfunction, autophagy-lysosomal system disorders, and neuroinflammation.
There is still a lack of effective drug treatments.
The search for new and effective drugs and mechanisms has important clinical significance for intervention in DA neuronal degeneration.
Recently, Zhang Yunlong's research group from the School of Basic Medical Sciences of Guangzhou Medical University, in conjunction with the Li Shiying's research group of the School of Pharmacy and Xu Pingyi's research group of the First Affiliated Hospital, designed and synthesized a "Trojan horse" drug delivery system (RVG-nDMC) that crosses the blood-brain barrier.
For the targeted delivery of flavonoids-4,4'-dimethoxychalcone (DMC) to dopamine neurons in the substantia nigra of the midbrain.
Studies have shown that RVG-nDMC can efficiently penetrate the blood-brain barrier and be taken up by DA neurons, and improve the motor deficit and DA neuron death in PD model mice.
The study combined RNA-sequencing, metabolomics and electron microscopy, and found that RVG-nDMC can inhibit the ubiquitination and degradation of the PD model dopamine synthesis rate-limiting enzyme—tyrosine hydroxylase (TH), and promote black DA neurons Synthesize dopamine and reduce the oxidative stress damage of DA neurons caused by ubiquitinated TH.
In addition, RVG-nDMC can also be taken up by substantia nigra microglia, and reduce the damage of neuroinflammation to DA neurons through anti-inflammatory effects.
RVG-nDMC showed no toxic and side effects on various organ systems.
This study reveals the new neuropharmacological mechanism of DMC against PD, and also provides a new idea for the treatment and intervention of PD.
Related results were published in Advanced Science.
Zhang Yunlong of the School of Basic Medical Sciences, Li Shiying of the School of Pharmacy, and Xu Pingyi of the First Affiliated Hospital are the corresponding authors of the paper.
Doctoral student Zhang Wenlong, experimentalist Chen Huaqing, master students Ding Liuyan and Gong Junwei are the co-first authors of the paper.
The research was supported by the National Natural Science Foundation of China, the National Key R&D Program, the Guangzhou Science and Technology Plan Project, and the Guangzhou Medical University Research Startup Fund.
WILEY paper information: Trojan Horse Delivery of 4,4′-Dimethoxychalcone for Parkinsonian NeuroprotectionWenlong Zhang, Huaqing Chen, Liuyan Ding,Junwei Gong, Mengran Zhang, Wenyuan Guo,Pingyi Xu, Shiying Li, Yunlong ZhangAdvanced ScienceDOI: 10.
1002/advs.
202004555 click "Read the original text" in the lower left corner to view the original text of the paper.
Introduction to AdvancedScience Journal "Advanced Science" (Advanced Science) Wiley is a high-quality open source journal founded in 2014.
It publishes innovative achievements and cutting-edge progress in various fields such as materials science, physical chemistry, biomedicine, and engineering.
The journal is dedicated to disseminating scientific research results to the public to the greatest extent, and all articles are freely available.
The latest impact factor is 15.
840, and the 2020 SCI journals of the Chinese Academy of Sciences will be divided into the Q1 area of the material science category and the Q1 area of the engineering technology category. Press and hold the QR code on the official WeChat platform of AdvancedScienceNewsWiley's scientific research information.
Follow us to share cutting-edge information|Focus on scientific research trends to publish scientific research news or apply for information sharing, please contact: ASNChina@Wiley.
com