ACS Chemical Neuroscience最新文献_第2页

Targeted Metabolomics for the Analysis of p-Cresol in Mouse Brain: Impact of Biological Sex and Strain. 小鼠脑内对甲酚的代谢组学分析：生物性别和品系的影响。

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2025-01-19 DOI: 10.1021/acschemneuro.4c00698

Laura Bertarini, Federico Imbeni, Antonietta Vilella, Silvia Alboni, Federica Pellati

{"title":"Targeted Metabolomics for the Analysis of p-Cresol in Mouse Brain: Impact of Biological Sex and Strain.","authors":"Laura Bertarini, Federico Imbeni, Antonietta Vilella, Silvia Alboni, Federica Pellati","doi":"10.1021/acschemneuro.4c00698","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00698","url":null,"abstract":"p-Cresol, an environmental contaminant and endogenous metabolite derived primarily from the conversion of l-tyrosine by intestinal microflora, is gaining increasing attention, due to its potential impact on human health. Recent studies have highlighted elevated levels of p-cresol and its metabolites, including p-cresyl sulfate and p-cresyl glucuronide, in various populations, suggesting a correlation with neurodevelopmental and neurodegenerative conditions. While the role of this compound as a uremic toxin is well established, its presence and concentration within the central nervous system (CNS) remain largely unexplored. To address this gap, an high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method was optimized and validated for the first time in this work for the targeted metabolomics of p-cresol in brain tissues. This method enabled the quantification of this compound in different brain areas of adult male and female C57BL/6J mice and in the cortex of various mouse strains, including CD-1 and the idiopathic autism model BTBR T+Itpr3tf/J. Additionally, preliminary analyses of human cortex samples confirmed the presence of p-cresol, suggesting its relevance in human brain health. Moreover, metabolomic analyses have further explored the correlations between p-cresol and neurotransmitters, with a particular focus on dopaminergic and noradrenergic pathways. These findings pave the way for understanding the potential impact of p-cresol on neurochemical networks and its implications for neurodevelopmental and neurodegenerative disorders.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reactivity of Olanzapine and Tricyclic Antidepressants on the Protective Effects of Trolox on Lipid Peroxidation Evaluated Using Fluorescence Anisotropy, Electron Paramagnetic Resonance Spectrometry, and Thermal Analysis. 利用荧光各向异性、电子顺磁共振光谱和热分析评价奥氮平和三环抗抑郁药对曲洛克斯脂质过氧化保护作用的反应性。

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2025-01-17 DOI: 10.1021/acschemneuro.4c00702

Yusuke Horizumi, Reo Tanada, Yuya Kurosawa, Miwa Takatsuka, Tomohiro Tsuchida, Satoru Goto

{"title":"Reactivity of Olanzapine and Tricyclic Antidepressants on the Protective Effects of Trolox on Lipid Peroxidation Evaluated Using Fluorescence Anisotropy, Electron Paramagnetic Resonance Spectrometry, and Thermal Analysis.","authors":"Yusuke Horizumi, Reo Tanada, Yuya Kurosawa, Miwa Takatsuka, Tomohiro Tsuchida, Satoru Goto","doi":"10.1021/acschemneuro.4c00702","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00702","url":null,"abstract":"Multiacting receptor-targeting antipsychotics and tricyclic antidepressants stimulate various neurotransmitter receptors despite the different targets of postsynaptic receptors and presynaptic reuptake transporters. Their auxiliary and adverse effects may be caused by multiple targets or the modification of the neuronal membrane. To evaluate the membrane responses to olanzapine, imipramine, desipramine, amitriptyline, lidocaine, and dibucaine, we examined the inhibition of lipid peroxidation in egg yolk phosphatidylcholine liposomes. By contrast, their effects on membrane fluidity were measured as the suppressive contributions of the inhibitory activity of Trolox on lipid oxidation. These drugs inhibit lipid peroxidation and exclude harmful reactive oxygen species and the protective effect of Trolox. The fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene in saturated phospholipid liposome-containing drugs suggested that olanzapine, imipramine, and dibucaine enhanced membrane fluidity. The radical scavenging activity of 2,2-diphenylpicrylhidrazyl and galvinoxyl radicals was determined using electron paramagnetic resonance experiments, and their molecular flexibility was determined using thermograms for differential scanning calorimetry. Multiple regression analyses of the linear free energy relationship approach and comparative investigations revealed that the membranous fluidity of the liposomes, independent of the radical scavenging activity of the drugs, induced the inhibitory activity on lipid peroxidation. We discussed how these drugs act on nervous membranes and aimed to identify the relationship between uncertified functions and membranous fluidity.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel Dual-Functional Half-Curcumin Analogues as a Fluorescent and PET Probe for β-Amyloid Imaging in the Alzheimer's Disease APP/PS1 Model. 新型双功能半姜黄素类似物作为阿尔茨海默病APP/PS1模型β-淀粉样蛋白成像的荧光和PET探针

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2025-01-17 DOI: 10.1021/acschemneuro.4c00532

Haijun Yang, Ke Li, Tingfang Wang, Yi Zou, Guanyu Xu, Can Zhou, Zeying Liang, Yingqiu Wang, Jianguo Lin, Jian Yang

{"title":"Novel Dual-Functional Half-Curcumin Analogues as a Fluorescent and PET Probe for β-Amyloid Imaging in the Alzheimer's Disease APP/PS1 Model.","authors":"Haijun Yang, Ke Li, Tingfang Wang, Yi Zou, Guanyu Xu, Can Zhou, Zeying Liang, Yingqiu Wang, Jianguo Lin, Jian Yang","doi":"10.1021/acschemneuro.4c00532","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00532","url":null,"abstract":"Noninvasive imaging of β-amyloid in vivo is pivotal for the early diagnosis of Alzheimer's disease (AD). While single imaging methods have been extensively studied for detecting Aβ over the past decade, dual-modal probes have received scant attention. In this study, we synthesized and assessed a series of half-curcumin probes, among which DiFboron-8 demonstrated a high affinity and selectivity for Aβ aggregates. DiFboron-8 effectively served as a dual-functional fluorescent and positron emission tomography (PET) probe for imaging β-amyloid in an AD mouse model. Histological staining results underscored DiFboron-8's potent staining capability for Aβ plaques in APP/PS1 brain slices, while ex vivo biodistribution studies highlighted its rapid clearance rate. In vivo imaging revealed that [18F]-DiFboron-8 could penetrate the blood-brain barrier, displaying higher PET signals in the brains of APP/PS1 mice compared to wild-type mice just 3 min postinjection, a finding corroborated by autoradiography staining. Overall, we propose that [18F]-DiFboron-8 represents an efficient fluorescent/PET dual-modal probe, offering promise for β-amyloid imaging in the early stages of AD.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigation of the Effects of Light, Darkness, and Dim Light on Rat Brain Tissue: A Biochemical and Histological Study. 光、暗、弱光对大鼠脑组织影响的生化和组织学研究。

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2025-01-17 DOI: 10.1021/acschemneuro.4c00757

Hıdır Pekmez, Tuğba Raika Kıran, Fahriye Seçil Tecelli Oğlu, Feyza İnceoğlu, Merve Aydin, Emrah Zayman, Sinan Canpolat

{"title":"Investigation of the Effects of Light, Darkness, and Dim Light on Rat Brain Tissue: A Biochemical and Histological Study.","authors":"Hıdır Pekmez, Tuğba Raika Kıran, Fahriye Seçil Tecelli Oğlu, Feyza İnceoğlu, Merve Aydin, Emrah Zayman, Sinan Canpolat","doi":"10.1021/acschemneuro.4c00757","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00757","url":null,"abstract":"This study evaluates acetylcholinesterase (AChE) enzyme activity levels, oxidative stress parameters, histopathological findings, and serum melatonin levels in rat brain tissue. 32 male Wistar Albino rats were randomly divided into four groups: Control, Light, Dark, Dim light (n = 8 each group). After a 30 day experiment, brain tissues were collected to measure AChE, glutathione S-transferase (GST), glutathione (GSH), and malondialdehyde (MDA) levels and conduct histopathological analyses. Serum melatonin levels were also measured. In this study, we observed a significant increase in MDA levels in dim light, dark, and light groups. AChE and α-GST enzyme activity levels were significantly decreased in the dark group compared with the other groups. Additionally, there was a statistical difference in melatonin levels between the light and dark groups. In the light microscope examination of the sections stained with hematoxylin-eosin from the dark group brain tissue, mild perineuronal edema was observed in all areas. Our study is the first to compare the effects of three groups on the brain: continuous light, continuous darkness, and dim light at night. Additionally, it is the only study to examine the effects of light exposure differences on the brain AChE levels.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142995996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Insight into the Structure of the Neutral Amino Acid Transporter B⁰AT2 Enabled the Discovery of Tiagabine as an Inhibitor. 对中性氨基酸转运体B0AT2结构的深入研究，发现了Tiagabine作为抑制剂。

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2025-01-15 Epub Date: 2024-12-27 DOI: 10.1021/acschemneuro.4c00800

Jędrzej Kukułowicz, Agata Siwek, Małgorzata Wolak, Angelika Bröer, Aditya Yadav, Stefan Bröer, Marek Bajda

{"title":"Insight into the Structure of the Neutral Amino Acid Transporter B0AT2 Enabled the Discovery of Tiagabine as an Inhibitor.","authors":"Jędrzej Kukułowicz, Agata Siwek, Małgorzata Wolak, Angelika Bröer, Aditya Yadav, Stefan Bröer, Marek Bajda","doi":"10.1021/acschemneuro.4c00800","DOIUrl":"10.1021/acschemneuro.4c00800","url":null,"abstract":"The sodium-dependent membrane transporter SLC6A15 (B0AT2) belongs to the SLC6 family, which comprises carriers of amino acids and monoamines. B0AT2 is expressed in the central nervous system (CNS), including the glutaminergic and GABAergic system. SLC6A15 supplies neurons with neutral amino acids. Its main substrates, branched-chain amino acids, and proline serve for glutamate biosynthesis, whereas silencing of B0AT2 leads to lower levels of neuronal glutamate. Recent research revealed that polymorphisms in the vicinity of slc6a15 are associated with major depressive disorder and anxiety. Mouse B0AT2 knockouts, by contrast, showed an antianxiety feature. Applying computational tools, we constructed models of B0AT2. Their structure was discussed extensively, enabling insight into the determinants of transport mechanism and substrate selectivity. Understanding the molecular basis of the B0AT2 inhibition by loratadine led to the discovery of a new inhibitor that is tiagabine, an anticonvulsant drug prescribed off-label in the treatment of anxiety and possessing antidepressant features. The results showed that tiagabine appears to have a higher affinity to the transporter than loratadine, which is the most potent inhibitor to date. Our findings support the development of new B0AT2 inhibitors that could be useful for investigating their therapeutic relevance, while the identification of tiagabine as a novel SLC6A15 inhibitor adds a new dimension to the pharmacological complexity of this drug.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":"262-274"},"PeriodicalIF":4.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Opposite Roles of Cholesterol and Lanosterol in Lipid Membrane on Amyloid-Beta 42 Peptide Nucleation and Fibril Formation. 脂膜中胆固醇和羊毛甾醇在淀粉样β 42肽成核和纤维形成中的相反作用。

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2025-01-15 Epub Date: 2024-12-21 DOI: 10.1021/acschemneuro.4c00707

Kyohei Akiho, Akane Iida-Adachi, Hideki Nabika

{"title":"Opposite Roles of Cholesterol and Lanosterol in Lipid Membrane on Amyloid-Beta 42 Peptide Nucleation and Fibril Formation.","authors":"Kyohei Akiho, Akane Iida-Adachi, Hideki Nabika","doi":"10.1021/acschemneuro.4c00707","DOIUrl":"10.1021/acschemneuro.4c00707","url":null,"abstract":"Molecular self-assembly of amyloid-beta peptides to form fibrillar aggregates is a known cause of Alzheimer's disease. Although homogeneous nucleation of amyloid-beta is unfavorable, heterogeneous nucleation of amyloid-beta in cell membranes plays a key role in fibril formation. We observed these opposite roles in the effects of cholesterol and lanosterol, the precursor of cholesterol in the brain, on nucleation. As previously reported, cholesterol accelerated nucleation, whereas lanosterol decelerated it when mixed with dioleoyl-phosphatidylcholine at 20%. The observed opposite effects of cholesterol and lanosterol on nucleation do not correlate with the differences in the mechanical and thermodynamic nature of mixed membranes. However, the affinity of amyloid-beta to the inner membrane seems to be related to the opposite effects on nucleation kinetics. Cholesterol reduced the insertion of amyloid-beta into the lipid membrane, whereas lanosterol promoted the insertion of amyloid-beta into the membrane, which would make amyloid-beta more tightly bound by lipid molecules and reduce its diffusivity in the membrane and consequently inhibit nucleation. Our study provides insights into the effects of sterol compounds other than the well-investigated cholesterol on the self-assembly of amyloid-beta to clarify the molecular basis underlying Alzheimer's disease pathology and to develop targeted therapeutic strategies.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":"195-202"},"PeriodicalIF":4.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development and Evaluation in Rat and Monkey of a Candidate Homochiral Radioligand for PET Studies of Brain Receptor Interacting Protein Kinase 1: [¹⁸F](S)-1-(5-(3-Fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-2,2-dimethylpropan-1-one. 脑受体相互作用蛋白激酶1候选同手性放射配体的研制及在大鼠和猴子中的评价：[18F](S)-1-（5-（3-氟苯基）-4,5-二氢- 1h -吡唑-1-基）-2,2-二甲基丙烷-1- 1。

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2025-01-15 Epub Date: 2025-01-02 DOI: 10.1021/acschemneuro.4c00715

Susovan Jana, Mudasir Maqbool, Xuefeng Yan, Jimmy E Jakobsson, Adrian C Lee, Jeih-San Liow, Sami S Zoghbi, Shawn Wu, Priscilla Long, Robert B Innis, Sanjay Telu, Victor W Pike

{"title":"Development and Evaluation in Rat and Monkey of a Candidate Homochiral Radioligand for PET Studies of Brain Receptor Interacting Protein Kinase 1: [18F](S)-1-(5-(3-Fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-2,2-dimethylpropan-1-one.","authors":"Susovan Jana, Mudasir Maqbool, Xuefeng Yan, Jimmy E Jakobsson, Adrian C Lee, Jeih-San Liow, Sami S Zoghbi, Shawn Wu, Priscilla Long, Robert B Innis, Sanjay Telu, Victor W Pike","doi":"10.1021/acschemneuro.4c00715","DOIUrl":"10.1021/acschemneuro.4c00715","url":null,"abstract":"Receptor interacting protein kinase 1 (RIPK1) crucially upregulates necroptosis and is a key driver of inflammation. An effective PET radioligand for imaging brain RIPK1 would be useful for further exploring the role of this enzyme in neuroinflammation and for assisting drug discovery. Here, we report our progress on developing a PET radioligand for RIPK1 based on the phenyl-1H-dihydropyrazole skeleton of a lead RIPK1 inhibitor, GSK'963. The most potent inhibitor from a small structure-activity relationship study,(S)-1-(5-(3-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-2,2-dimethylpropan-1-one ((S)-SJ1058 or (S)-5d), was labeled with no-carrier-added fluorine-18 (t1/2 = 109.8 min) from a homochiral meta-tri-n-butylstannane precursor [(S)-11c] in 10-15% formulated yields. The lipophilicity measured for [18F](S)-SJ1058 was moderate (log D7.4 = 3.00) and conducive to good brain permeability. PET scans with [18F](S)-SJ1058 in healthy monkeys under baseline and preblock conditions with a RIPK1 inhibitor, either Nec-1s or GSK'963, demonstrated high peak radioactivity uptake in the brain (3.1-3.9 SUV) but no evidence of in vivo RIPK1-specific binding. Moreover, [18F](S)-SJ1058 did not detect neuroinflammation in rats on day 1 and day 8 after systemic lipopolysaccharide administration. We conclude that [18F](S)-SJ1058 is unpromising for imaging human brain RIPK1 in neuroinflammation. Higher-affinity radioligands may be needed for this purpose.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":"203-222"},"PeriodicalIF":4.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neurofilament Light Chain under the Lens of Structural Mass Spectrometry. 结构质谱透镜下的神经丝轻链。

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2025-01-15 Epub Date: 2025-01-02 DOI: 10.1021/acschemneuro.4c00526

Salomé Coppens, Dea Gogishvili, Valentina Faustinelli, Emanuele Scollo, Christopher Hopley, Sanne Abeln, Paul Dalby, Heidi Goenaga-Infante, Luise Luckau, Jérôme Vialaret, Sylvain Lehmann, Christophe Hirtz, Eva Illes-Toth

{"title":"Neurofilament Light Chain under the Lens of Structural Mass Spectrometry.","authors":"Salomé Coppens, Dea Gogishvili, Valentina Faustinelli, Emanuele Scollo, Christopher Hopley, Sanne Abeln, Paul Dalby, Heidi Goenaga-Infante, Luise Luckau, Jérôme Vialaret, Sylvain Lehmann, Christophe Hirtz, Eva Illes-Toth","doi":"10.1021/acschemneuro.4c00526","DOIUrl":"10.1021/acschemneuro.4c00526","url":null,"abstract":"Neurofilament light chain (NfL) is an early nonspecific biomarker in neurodegenerative diseases and traumatic brain injury, indicating axonal damage. This work describes the detailed structural characterization of a selected primary calibrator with the potential to be used in future reference measurement procedure (RMP) development for the accurate quantification of NfL. As a part of the described workflow, the sequence, higher-order structure as well as solvent accessibility, and hydrogen-bonding profile were assessed under three different conditions in KPBS, artificial cerebrospinal fluid, and artificial cerebrospinal fluid in the presence of human serum albumin. The results revealed that NfL is a structurally heterogeneous protein, eliciting a large conformational flexibility. Its structural ensemble changed when it was diluted with an aqueous buffer versus a surrogate matrix, artificial cerebrospinal fluid (aCSF), and/or aCSF with human serum albumin. Various regions of protection and deprotection in the protein head, central helical, and tail domains that experienced altered solvent accessibility and conformational changes caused by different solvent conditions were identified. Moreover, interfacial residues, which may play a role in a potential direct interaction between NfL and human serum albumin, emerged from hydrogen-deuterium exchange mass spectrometry (HDX-MS). These data pinpointed distinct regions of the protein that may participate in such an interaction. Overall, critical quality attributes of a potential primary calibrator for NfL measurements are provided. These findings will ultimately inform ongoing biochemical and clinical assay development procedures and manufacturing practices, giving careful consideration during sample handling and method development.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":" ","pages":"141-151"},"PeriodicalIF":4.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142918806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Visualizing Endoplasmic Reticulum Stress and Autophagy in Alzheimer's Model Cells by a Peroxynitrite-Responsive AIEgen Fluorescent Probe. 用过氧亚硝酸盐反应型aigen荧光探针观察阿尔茨海默病模型细胞的内质网应激和自噬。

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2025-01-15 Epub Date: 2025-01-06 DOI: 10.1021/acschemneuro.4c00770

Lushan Huang, Liyi Ma, Qichen Zhu, Hongyuan Wang, Guangwei She, Wensheng Shi, Lixuan Mu

{"title":"Visualizing Endoplasmic Reticulum Stress and Autophagy in Alzheimer's Model Cells by a Peroxynitrite-Responsive AIEgen Fluorescent Probe.","authors":"Lushan Huang, Liyi Ma, Qichen Zhu, Hongyuan Wang, Guangwei She, Wensheng Shi, Lixuan Mu","doi":"10.1021/acschemneuro.4c00770","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00770","url":null,"abstract":"Endoplasmic reticulum (ER) stress and autophagy (ER-phagy) occurring in nerve cells are crucial physiological processes closely associated with Alzheimer's disease (AD). Visualizing the two processes is paramount to advance our understanding of AD pathologies. Among the biomarkers identified, peroxynitrite (ONOO-) emerges as a key molecule in the initiation and aggravation of ER stress and ER-phagy, highlighting its significance in the underlying mechanisms of the two processes. In this work, we designed and synthesized an innovative ONOO--responsive AIEgen-based fluorescent probe (DHQM) with the ability to monitor ER stress and ER-phagy in AD model cells. DHQM demonstrated excellent aggregation-induced emission (AIE) properties, endowing it with outstanding ability for washing-free intracellular imaging. Meanwhile, it exhibited high sensitivity, remarkable selectivity to ONOO-, and exceptional ER-targeting ability. The probe was successfully applied for fluorescence imaging of ER ONOO- fluctuations to assess the ER stress status in aluminum-induced AD model cells. Our findings revealed that aluminum-induced ferroptosis, a regulated cell death process, was pivotal in the excessive ONOO- production, which in turn activated and exacerbated ER stress. Furthermore, the aluminum-stimulated ER-phagy was observed utilizing DHQM, which might be crucial in inhibiting ferroptosis and mitigating aberrant ER stress. Overall, this study not only offers valuable insights into the pathological mechanisms of AD at the ER level but also opens new potential therapeutic avenues targeting these pathways.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"16 2","pages":"223-231"},"PeriodicalIF":4.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cocaine-Induced Remodeling of the Rat Brain Peptidome: Quantitative Mass Spectrometry Reveals Anatomically Specific Patterns of Cocaine-Regulated Peptide Changes. 可卡因诱导的大鼠脑肽丘重塑：定量质谱法揭示了可卡因调节的肽变化的解剖特异性模式。

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2025-01-15 Epub Date: 2024-12-31 DOI: 10.1021/acschemneuro.4c00327

Gaoyuan Lu, Fengfei Ma, Pingli Wei, Min Ma, Vu Ngoc Huong Tran, Brian A Baldo, Lingjun Li

{"title":"Cocaine-Induced Remodeling of the Rat Brain Peptidome: Quantitative Mass Spectrometry Reveals Anatomically Specific Patterns of Cocaine-Regulated Peptide Changes.","authors":"Gaoyuan Lu, Fengfei Ma, Pingli Wei, Min Ma, Vu Ngoc Huong Tran, Brian A Baldo, Lingjun Li","doi":"10.1021/acschemneuro.4c00327","DOIUrl":"10.1021/acschemneuro.4c00327","url":null,"abstract":"Addiction to psychostimulants, including cocaine, causes widespread morbidity and mortality and is a major threat to global public health. Currently, no pharmacotherapies can successfully treat psychostimulant addiction. The neuroactive effects of cocaine and other psychostimulants have been studied extensively with respect to their modulation of monoamine systems (particularly dopamine); effects on neuropeptide systems have received less attention. Here, we employed mass spectrometry (MS) methods to characterize cocaine-induced peptidomic changes in the rat brain. Label-free peptidomic analysis using liquid chromatography coupled with tandem MS (LC-MS/MS) was used to describe the dynamic changes of endogenous peptides in five brain regions (nucleus accumbens, dorsal striatum, prefrontal cortex, amygdala, and hypothalamus) following an acute systemic cocaine challenge. The improved sensitivity and specificity of this method, coupled with quantitative assessment, enabled the identification of 1376 peptides derived from 89 protein precursors. Our data reveal marked, region-specific changes in peptide levels in the brain induced by acute cocaine exposure, with peptides in the cholecystokinin and melanin-concentrating hormone families being significantly affected. These findings offer new insights into the region-specific effects of cocaine and could pave the way for developing new therapies to treat substance use disorders and related psychiatric conditions.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"16 2","pages":"128-140"},"PeriodicalIF":4.1,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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