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
PHYSIOLOGY & BEHAVIOR
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2019
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IF 2.635
Panwen Liu,Lingyu Cui,Bo Liu,Weiwei Liu,Toshihiko Hayashi,Kazunori Mizuno,Shunji Hattori,Yuko Ushiki-Kaku,Satoshi Onodera,Takashi Ikejima
Alzheimer's disease (AD) is a neurodegenerative disease, mainly characterized by cognitive dysfunction and memory impairment. Due to its pathological similarities to type 2 diabetes mellitus (T2DM), such as β-amyloid deposition, oxidative stress, inflammation, disordered glucose metabolism, impaired signaling pathways of insulin and insulin-like growth factor-1 (IGF-1), we speculate that AD is another form of brain diabetes. Clarifying the relationship between T2DM and AD is important for us to better understand the exact pathological mechanisms of AD. Silibinin, a polyphenolic flavonoid extracted from the seeds of Silybum marianum , exerts hepatoprotective, anti- diabetic and neuroprotective effects. Streptozotocin (STZ), which is used to disrupt the insulin signal transduction pathway, could well mimic the sporadic AD models by intracerebroventricular (ICV) injection. Therefore, we selected ICV injection of STZ (ICV-STZ) to investigate the neuroprotective effects of silibinin in rats and to make a foundation for further exploring the relationship between AD and T2DM. ICV-STZ obviously caused memory damage, sharply reduced the number of nissl bodies and destroyed morphological structure of hippocampal neuronal cells, while silibinin attenuated the damages. Moreover, silibinin significantly decreased STZ-induced tau hyperphosphorylation (ser404) in hippocampus and cerebral cortex, markedly inhibited apoptosis of neurons induced by STZ, and up-regulated insulin signal transduction pathway. Silibinin exerts neuroprotective effect in STZ-treated rats, indicating the potential of silibinin for the treatment of AD patients with T2DM in future.
研究领域:
神经科学
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药理学
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内分泌学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
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2022
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IF 6.656
Chang-Long He,Yong Tang,Xue Chen,Tao Long,Yan-Ni He,Jing Wei,Jian-Ming Wu,Cai Lan,Lu Yu,Fei-Hong Huang,Cong-Wei Gu,Jian Liu,Chong-Lin Yu,Vincent Kam-Wai Wong,Betty Yuen-Kwan Law,Da-Lian Qin,An-Guo Wu,Xiao-Gang Zhou
Background Protein aggregates are considered key pathological features in neurodegenerative diseases (NDs). The induction of autophagy can effectively promote the clearance of ND-related misfolded proteins. Objective In this study, we aimed to screen natural autophagy enhancers from traditional Chinese medicines (TCMs) presenting potent neuroprotective potential in multiple ND models. Methods The autophagy enhancers were broadly screened in our established herbal extract library using the transgenic Caenorhabditis elegans ( C. elegans ) DA2123 strain. The neuroprotective effects of the identified autophagy enhancers were evaluated in multiple C. elegans ND models by measuring Aβ-, Tau-, α-synuclein-, and polyQ40-induced pathologies. In addition, PC-12 cells and 3 × Tg-AD mice were employed to further validate the neuroprotective ability of the identified autophagy enhancers, both in vitro and in vivo . Furthermore, RNAi bacteria and autophagy inhibitors were used to evaluate whether the observed effects of the identified autophagy enhancers were mediated by the autophagy-activated pathway. Results The ethanol extract of Folium Hibisci Mutabilis (FHME) was found to significantly increase GFP::LGG-1-positive puncta in the DA2123 worms. FHME treatment markedly inhibited Aβ , α-synuclein, and polyQ40, as well as prolonging the lifespan and improving the behaviors of C. elegans , while siRNA targeting four key autophagy genes partly abrogated the protective roles of FHME in C. elegans . Additionally, FHME decreased the expression of AD-related proteins and restored cell viability in PC-12 cells, which were canceled by cotreatment with 3-methyladenine (3-MA) or bafilomycin A1 (Baf). Moreover, FHME ameliorated AD-like cognitive impairment and pathology, as well as activating autophagy in 3 × Tg-AD mice. Conclusion FHME was successfully screened from our natural product library as a potent autophagy enhancer that exhibits a neuroprotective effect in multiple ND models across species through the induction of autophagy. These findings offer a new and reliable strategy for screening autophagy inducers, as well as providing evidence that FHME may serve as a possible therapeutic agent for NDs.
研究领域:
神经科学
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药理学
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中药
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自噬研究
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神经退行性疾病
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产品关联
DOI
PubMed
高影响因子
PSYCHOPHARMACOLOGY
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2024
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IF 3.5
Liu Xin,Jin Yongzeng,Cheng Xinyi,Song Qinghua,Wang Yanan,He Ling,Chen Tong
Rationale The plasma ceramide levels in Alzheimer’s disease (AD) patients are found abnormally elevated, which is related to cognitive decline. Objectives This research was aimed to investigate the mechanisms of aberrant elevated ceramides in the pathogenesis of AD. Results The ICR mice intracerebroventricularly injected with Aβ 1-42 and APP/PS1 transgenic mice were employed as AD mice. The cognitive deficiency, impaired episodic and spatial memory were observed without altered spontaneous ability. The serum levels of p-tau and ceramide were evidently elevated. The modified expressions and activities of glycogen synthase kinase-3β (GSK-3β) and protein phosphatase 2A (PP2A) influenced the serum content of p-tau. The levels of ceramide synthesis-related genes including sptlc1, sptlc2, cers2, and cers6 in the liver of AD mice were increased, while the ceramide degradation-related gene asah2 did not significantly change. The regulations of these genes were conducted by activated nuclear factor kappa-B (NF-κB) signaling. NF-κB, promoted by free fatty acid (FFA), also increased the hepatic concentrations of proinflammatory cytokines. The FFA amount was modulated by fatty acid synthesis-related genes acc1 and srebp-1c. Besides, the decreased levels of pre-proopiomelanocortin (pomc) mRNA and increased agouti-related protein (agrp) mRNA were found in the hypothalamus without significant alteration of melanocortin receptor 4 (MC4R) mRNA. The bioinformatic analyses proved the results using GEO datasets and AlzData. Conclusions Ceramide was positively related to the increased p-tau and impaired cognitive function. The increased generation of ceramide and endoplasmic reticulum stress in the hypothalamus was positively related to fatty acid synthesis and NF-κB signaling via brain–liver axis.
研究领域:
神经科学
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药理学
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分子生物学
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病理学
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DOI
PubMed
高影响因子
NEUROSCIENCE LETTERS
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2024
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IF 2.5
Xiyong Xiang,Siyu Xia,Shan Li,Yirong Zeng,Lixuan Wang,Yan Zhou
The occurrence and development of Alzheimer’s disease (AD) is closely related to neuronal loss, inflammatory response, cholinergic imbalance, and Tau protein hyperphosphorylation. Previous studies have confirmed that Streptozotocin (STZ) can be used to establish a rat model of AD by injecting it into the rat brain via the lateral ventricle. Our previous research showed that Danshentone IIA (Tan IIA) can improve cognitive dysfunction in rats caused by CC chemokine ligand 2, and network pharmacology results show that Tan IIA is very likely to improve AD symptoms through the cyclic adenosine monophosphate response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), and tyrosine kinase receptor protein (TrkB) pathway. The results of the water maze experiment showed that after Tan IIA treatment, the escape latency of AD rats was shortened and the number of platform crossings increased; in the new object recognition experiment, the discrimination index of AD rats significantly increased after treatment; Nissl staining and Tunel staining results showed that Tan IIA increased the number of surviving neurons in the hippocampus of cognitively impaired rats and reduced neuronal apoptosis; Bielschowsky silver staining results showed that Tan IIA reduced neurofibrillary tangles (NFTs) in the AD rats; Tan IIA can reduce the inflammatory response and oxidative stress reaction in the hippocampus of AD rats, and at the same time reduce the activity of acetylcholinesterase. Tan IIA can significantly increase the expression of CREB, BDNF, TrkB in the hippocampal tissue of STZ-injured rats (P < 0.05). These data suggest that Tan IIA may upregulate the expression of the CREB-BDNF-TrkB signaling pathway in the hippocampus of brain tissue, produce anti-neuroinflammatory, antioxidant stress, inhibit neuronal apoptosis effects, and improve cholinergic neurotransmitter disorder induced by STZ, reduce the neuronal damage and learning and memory impairment caused by STZ in rats, and improve the cognitive function of rats.
研究领域:
神经科学
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药理学
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分子生物学
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神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
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2019
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IF 3.775
Wei Yang,Zhi-Kai Tian,Hui-Xin Yang,Zhao-Jun Feng,Jian-Mei Sun,Hong Jiang,Chao Cheng,Qing-Lei Ming,Chan-Min Liu
Fisetin , a natural flavonoid found in plants, fruits and vegetables, exerts anti-cancer, anti-oxidant, anti-inflammatory and anti-mitotic effects. The current study instigates the protective effect of fisetin against lead-induced synaptic dysfunction, neuroinflammation and neurodegeneration in mice, and explores its underlying mechanisms. The results indicated fisetin can significantly ameliorated behavioral impairments in Pb-treated mice. Fisetin inhibited Pb-induced the apoptotic neurodegeneration, as indicated by the decreased levels of Bax and cleaved caspase-3. Fisetin suppressed activations of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), NF-κB and subsequently inactivate pro-inflammatory factor including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). It can also decrease the accumulation of p-tau and amyloid-beta (Aβ) and increased the expression of the Aβ remover neprilysin (NEP) in brains of mice. Fisetin also reversed Pb-induced synaptic dysfunction by increasing the levels of synaptosomal associated protein-25 (SNAP-25), postsynaptic density-95 (PSD-95), cyclic-AMP-response element-binding protein (CREB) phosphorylation and calcium/calmodulin kinase II (CaMKII) phosphorylation. Fisetin promoted Pb-induced autophagy in the brains of mice. Moreover, fisetin can increase levels of the denosine 5′-monophosphate-activated protein kinase (AMPK) phosphorylation and SIRT1. Fisetin may be developed as a potential nutritional target for the prevention of Pb-induced neurotoxicity .
研究领域:
神经科学
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药理学
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毒理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）