CHEMICO-BIOLOGICAL INTERACTIONS
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2014
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IF 2.982
Zhaoguang Lu,Junsong Wang,Minghui Li,Qingwang Liu,Dandan Wei,Minghua Yang,Lingyi Kong
A goldfish ( Carassius auratus ) model of Parkinson’s disease (PD) was constructed by a single dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) according to previously reported methods. Global metabolite changes in brain of the MPTP induced goldfish model of PD were investigated. 1 H NMR-based metabolomics combined with various statistical methods such as orthogonal partial least squares discriminant analysis (OPLS-DA) and two-dimensional statistical total correlation spectroscopy (2D-STOCSY) found significant increase of leucine, isoleucine, valine, alanine, alanylalanine, creatinine, myo -inositol, 18:2 fatty acid, total fatty acids, arachic alcohol, taurine and significant decrease of N-acetylaspartate, (phospho)creatine, (phospho)choline, betaine, glutamine, 3-hexenedioate, acetamide, malonate, isocitrate, scyllo -inositol, phosphatidylcholines, cholesterols, n-3 fatty acids, polyunsaturated fatty acids (PUFAs) in brain of MPTP induced PD goldfish. These disturbed metabolite levels were involved in oxidative stress , energy failure, neuronal cell injury and death, consistent with those observed in clinical PD patients, and rodents and primates model of PD, indicating that the acute MPTP model of goldfish was an ideal and valuable model for PD research. In addition, several unusual metabolites in brain were significantly changed between MPTP induced PD and control goldfish, which might also play an important role in the pathogenesis of PD. This study also demonstrated the applicability and potential of 1 H NMR-based metabolomics approach for evaluation of animal models of disease induced by chemicals, such as MPTP-induced PD goldfish.
研究领域:
神经科学
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代谢组学
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毒理学
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产品关联
DOI
PubMed
高影响因子
Applied Materials Today
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2022
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IF 8.663
Lukuan Xie,Honglei Lin,Lingrui Lv,Wenxin Zhang,Feng Feng,Fulei Liu,Wenyuan Liu,Lingfei Han
Parkinson's disease (PD), one of common neurodegenerative diseases, afflicts many elderly people lacking of effective treatment strategies. Rhynchophylline (RIN) is an anti-PD natural active compound. However, RIN can hardly cross the blood-brain barrier (BBB) and is easily excreted as a substrate of P-glycoprotein (P-gp), making it difficult to exert anti-PD efficacy in brain. Nanocarrier-based brain targeting strategies provide an attractive platform to address brain distribution problems of drugs. In this work, we designed a brain-targeting core-shell nanoparticle (RIN/TAR-A2-CSN) for the programmed co-delivery of RIN and P-gp inhibitor Tariquidar (TAR). It was composed of Angiopep-2 (A2) modified reduction-responsive PEG shell material and thiamine disulfide system (TDS) grafted polyglutamate core material. After entering the body, first RIN/TAR-A2-CSN crossed the BBB into the brain via A2-receptor-mediated transport. Subsequently, the shell material disintegrated under reducing conditions, and the TDS-grafted core material was reduced to become hydrophilic, thereby leading to the drugs "locked-in" the brain. Finally, the released TAR inhibits P-gp-mediated RIN efflux, increases the retention time of RIN in the brain, and fully exerts the anti-PD effect of RIN. The brain targeting efficiency of RIN/TAR-A2-CSN was improved to 5.8 times that of free RIN. In addition, the therapeutic effect on the MPTP-induced PD mice model was significantly improved. This work develops a novel brain targeting strategy for drugs to overcome BBB and inhibit efflux. RIN/TAR-A2-CSN nanoparticles show the potential to become PD therapeutics.
研究领域:
神经药理学
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纳米技术
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药学
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神经退行性疾病
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产品关联
DOI
高影响因子
Advanced Science
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2025
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IF 14.1
Shuoting Zhou,Xi Xiong,Jialong Hou,Qi Duan,Yi Zheng,Tao Jiang,Jiani Huang,Haijun He,Jiaxue Xu,Keke Chen,Wenwen Wang,Jinlai Cai,Jingjing Qian,Huijun Chen,Weihong Song,XinShi Wang,Chenglong Xie
Serving as a pivotal hub for cellular metabolism and intracellular signaling, the mitochondrion has emerged as a crucial organelle whose dysfunction is linked to many human diseases, including neurodegenerative disorders, particularly Parkinson's disease (PD). However, whether mitochondrial quality control (MQC) can be targeted for therapeutic interventions remains uncertain. This study uses clinical samples, molecular biology techniques, pharmacological interventions, and genetic approaches to investigate the significance of NAD+ levels in cross-species models of PD. These results reveal that treatment of rotenone-incubated cells with NAD+ boosters (such as NMN, siCD38, and NAT) increases UPR mt /mitophagy-related MQC, reduces pro-inflammatory cytokine expression, inhibits apoptosis, and strengthen redox reactions. In vivo, NMN supplementation inhibits motor deficit and forestalls the neuropathological phenotypes of MPTP-induced PD mice, which are required for the atf4-related mitochondrial UPR pathway. Notably, bulk omics signatures and metabolomic profiling analyses of the striatum reveal NMN-induced transcriptional changes in genes and proteins involved in mitochondrial homeostasis. Thus, these findings demonstrate that the accelerated pathology in PD models is probably mediated by impaired MQC and that bolstering cellular NAD+ levels alleviates mitochondrial proteotoxic stress and mitigate PD phenotypes.
研究领域:
神经科学
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细胞生物学
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药理学
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分子生物学
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生物化学
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基因组学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2023
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IF 9.5
Xiaowei Cao,Shengjie Ge,Miao Chen,Haiyan Mao,Ying Wang
Multiplexed detection of Parkinson’s disease (PD) biomarkers is of great significance for early diagnosis and personalized treatment. In this study, we fabricated a robust surface-enhanced Raman scattering-enabled lab-on-a-chip (LoC-SERS) platform for simultaneous quantification of α-synuclein, phosphorylated tau protein 181, osteopontin, and osteocalcin. Herein, the antibody–DNA conjugate was designed to introduce the catalytic hairpin self-assembly (CHA) amplification into the protein detection. Au nano-stars (AuNSs) modified with Raman reporter molecules and hairpin-structure DNA 1 were applied as the SERS nanotags. Au-coated silicon nanocone array (Au/SiNCA) fabricated based on the maskless plasma etching-prepared high-density Si nanocone array (SiNCA) and surface ion sputtering was used as the capture substrate after the modification of hairpin-structure DNA 2. Benefitting from the antibody–DNA conjugate-induced CHA amplification, numerous AuNSs can be connected to the Au/SiNCA surface, which significantly amplify the plasmonic coupling effect for ultrasensitive SERS detection, and the limit of detection was less than the pg/mL level. The application of highly uniform Au/SiNCA and antibody–DNA conjugate endows the LoC-SERS platform excellent analytical performance, including superior reproducibility, satisfactory universality, and high sensitivity. In addition, a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice model was established, and satisfactory results were obtained in real sample analysis with the LoC-SERS platform, which may be enlightening for exploiting protein biomarkers in PD monitoring.
研究领域:
生物医学工程
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分析化学
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神经科学
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疾病诊断
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产品关联
DOI
PubMed
高影响因子
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