ACS Chemical Neuroscience最新文献_第10页

Kratom Alkaloids for the Treatment of Alcohol Use Disorder 克拉通生物碱治疗酒精使用障碍

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2024-11-29 DOI: 10.1021/acschemneuro.4c0067510.1021/acschemneuro.4c00675

Joydip Das*,

{"title":"Kratom Alkaloids for the Treatment of Alcohol Use Disorder","authors":"Joydip Das*, ","doi":"10.1021/acschemneuro.4c0067510.1021/acschemneuro.4c00675","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00675https://doi.org/10.1021/acschemneuro.4c00675","url":null,"abstract":"Alcohol use disorder (AUD) accounts for nearly 4.7% of all deaths and imposes a huge economic burden on society. Despite the magnitude of the problem, only a few Food and Drug Administration (FDA)/European Medicines Agency (EMA)-approved drugs are currently available for AUD treatment. Despite being efficacious, these drugs are not without problems, adverse effects being a major issue. That combined with medication adherence and compliance problems, the discovery of new drugs is imperative. Kratom (Mitragyna speciosa) alkaloids and some of their semisynthetic derivatives reduce alcohol intake and alcohol-induced withdrawal symptoms in animal models. These compounds act as G-protein-biased ligands at the μ-, δ-, and κ-opioid receptors, and their effect in reducing alcohol intake is mediated through the δ-opioid receptor. This article provides a critical overview of recent preclinical studies involving kratom alkaloids for AUD treatment, with a particular focus on the pharmacology and medicinal chemistry of these alkaloids. FDA/EMA approved drugs, repurposed drugs, and plant-based compounds for the treatment of AUD are briefly mentioned. Finally, important caveats and future research directions on this topic are discussed.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"15 24","pages":"4352–4359 4352–4359"},"PeriodicalIF":4.1,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142843787","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

Patent Review of Novel Biologics Targeting Opioid Use Disorder (2018–2024) 靶向阿片类药物使用障碍的新型生物制剂专利审查（2018-2024）

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2024-11-28 DOI: 10.1021/acschemneuro.4c0069110.1021/acschemneuro.4c00691

Samuel Obeng*, Lance R. McMahon and Edward Ofori*,

{"title":"Patent Review of Novel Biologics Targeting Opioid Use Disorder (2018–2024)","authors":"Samuel Obeng*, Lance R. McMahon and Edward Ofori*, ","doi":"10.1021/acschemneuro.4c0069110.1021/acschemneuro.4c00691","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00691https://doi.org/10.1021/acschemneuro.4c00691","url":null,"abstract":"Drug overdose deaths in 2023 in the United States exceeded 107,000, with 80,000 of these deaths attributed to opioids alone. The emergence of synthetic opioids such as fentanyl and its analogues have worsened the opioid overdose epidemic. A novel approach to treat opioid overdose and opioid use disorder (OUD) has been the introduction of biologics, which include monoclonal antibodies that bind to circulating opioids, preventing them from reaching the central nervous system, or peptides that have antinociceptive effects but lack the abuse liability of synthetic opioids. A challenge in the treatment of opioid overdose has been renarcotization, where an overdose patient revived with naloxone can re-enter an overdose state from residual opioid in the body. Biologics such as vaccines and monoclonal antibodies are excellent strategies that have been demonstrated to prevent renarcotization. In this review, we retrieved and discussed patents filed in the past six (6) years that focus on novel biologics reported as treatments for opioid overdose and OUD. We also provide a perspective on the use of biologics as therapeutics for OUD and opioid overdose.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"15 24","pages":"4360–4368 4360–4368"},"PeriodicalIF":4.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851105","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

From Nutritional Patterns to Behavior: High-Fat Diet Influences on Inhibitory Control, Brain Gene Expression, and Metabolomics in Rats 从营养模式到行为：高脂肪饮食对大鼠抑制控制、脑基因表达和代谢组学的影响

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2024-11-28 DOI: 10.1021/acschemneuro.4c0029710.1021/acschemneuro.4c00297

Diego Ruiz-Sobremazas, Ana Cristina Abreu, Ángeles Prados-Pardo, Elena Martín-González, Ana Isabel Tristán, Ignacio Fernández, Margarita Moreno and Santiago Mora*,

{"title":"From Nutritional Patterns to Behavior: High-Fat Diet Influences on Inhibitory Control, Brain Gene Expression, and Metabolomics in Rats","authors":"Diego Ruiz-Sobremazas, Ana Cristina Abreu, Ángeles Prados-Pardo, Elena Martín-González, Ana Isabel Tristán, Ignacio Fernández, Margarita Moreno and Santiago Mora*, ","doi":"10.1021/acschemneuro.4c0029710.1021/acschemneuro.4c00297","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00297https://doi.org/10.1021/acschemneuro.4c00297","url":null,"abstract":"Impulsive and compulsive behaviors are associated with inhibitory control deficits. Diet plays a pivotal role in normal development, impacting both physiology and behavior. However, the specific effects of a high-fat diet (HFD) on inhibitory control have not received adequate attention. This study aimed to explore how exposure to a HFD from postnatal day (PND) 33 to PND77 affects impulsive and compulsive behaviors. The experiment involved 40 Wistar rats subjected to HFD or chow diets. Several tasks were employed to assess behavior, including variable delay to signal (VDS), five choice serial reaction time task (5-CSRTT), delay discounting task (DDT), and rodent gambling task (rGT). Genetic analyses were performed on the frontal cortex, and metabolomics and fatty acid profiles were examined by using stool samples collected on PND298. Our results showed that the HFD group exhibited increased motor impulsive behaviors while not affecting cognitive impulsivity. Surprisingly, reduced impulsive decision-making was shown in the HFD group. Furthermore, abnormal brain plasticity and dopamine gene regulation were shown in the frontal cortex, while metabolomics revealed abnormal fatty acid levels.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"15 24","pages":"4369–4382 4369–4382"},"PeriodicalIF":4.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acschemneuro.4c00297","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142843949","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

Imidazo[2,1-b][1,3]thiazine Derivatives as Potential Modulators of Alpha-Synuclein Amyloid Aggregation 咪唑[2,1-b][1,3]噻嗪衍生物作为α -突触核蛋白淀粉样蛋白聚集的潜在调节剂

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2024-11-27 DOI: 10.1021/acschemneuro.4c0045110.1021/acschemneuro.4c00451

Indrė Misiu̅naitė, Kamilė Mikalauskaitė, Martyna Paulauskaitė, Ru̅ta Sniečkutė, Vytautas Smirnovas, Algirdas Brukštus, Mantas Žiaunys and Ieva Žutautė*,

{"title":"Imidazo[2,1-b][1,3]thiazine Derivatives as Potential Modulators of Alpha-Synuclein Amyloid Aggregation","authors":"Indrė Misiu̅naitė, Kamilė Mikalauskaitė, Martyna Paulauskaitė, Ru̅ta Sniečkutė, Vytautas Smirnovas, Algirdas Brukštus, Mantas Žiaunys and Ieva Žutautė*, ","doi":"10.1021/acschemneuro.4c0045110.1021/acschemneuro.4c00451","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00451https://doi.org/10.1021/acschemneuro.4c00451","url":null,"abstract":"Insoluble amyloid fibrils accumulate in the intercellular spaces of organs and tissues, leading to various amyloidosis-related disorders in the human body. Specifically, Parkinson’s disease is associated with the aggregation of alpha-synuclein. However, current treatments for Parkinson’s primarily focus on managing motor symptoms and slowing disease progression. Efforts to prevent and halt the progression of these diseases involve the search for small molecular compounds. In this work, we synthesized imidazo[2,1-b][1,3]thiazines in an atom-economic way by cyclization of 2-alkynylthioimidazoles using 10% AuCl as the catalyst. We identified several compounds with specific functional groups capable of both inhibiting the aggregation of alpha-synuclein and redirecting the fibril formation pathway. The investigation into how these substances function revealed that imidazo[2,1-b][1,3]thiazine derivatives can influence alpha-synuclein aggregation in several ways. They not only inhibit the primary nucleation process and maintain a balance toward nonaggregated protein states but also stabilize smaller oligomeric species of alpha-synuclein and cause the formation of fibrils with unique structures and forms. These imidazo[2,1-b][1,3]thiazines could potentially be used in developing highly efficient, small molecular weight protein aggregation inhibitors.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"15 24","pages":"4418–4430 4418–4430"},"PeriodicalIF":4.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acschemneuro.4c00451","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142843536","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

Investigating the Mechanism of Neurotoxic Effects of PFAS in Differentiated Neuronal Cells through Transcriptomics and Lipidomics Analysis 通过转录组学和脂质组学分析研究PFAS对分化神经细胞的神经毒性作用机制

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2024-11-27 DOI: 10.1021/acschemneuro.4c0065210.1021/acschemneuro.4c00652

Logan Running, Judith R. Cristobal, Charikleia Karageorgiou, Michelle Camdzic, John Michael N. Aguilar, Omer Gokcumen, Diana S. Aga* and G. Ekin Atilla-Gokcumen*,

{"title":"Investigating the Mechanism of Neurotoxic Effects of PFAS in Differentiated Neuronal Cells through Transcriptomics and Lipidomics Analysis","authors":"Logan Running, Judith R. Cristobal, Charikleia Karageorgiou, Michelle Camdzic, John Michael N. Aguilar, Omer Gokcumen, Diana S. Aga* and G. Ekin Atilla-Gokcumen*, ","doi":"10.1021/acschemneuro.4c0065210.1021/acschemneuro.4c00652","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00652https://doi.org/10.1021/acschemneuro.4c00652","url":null,"abstract":"Per- and polyfluorinated alkyl substances (PFAS) are pervasive environmental contaminants that bioaccumulate in tissues and pose risks to human health. Increasing evidence links PFAS to neurodegenerative and behavioral disorders, yet the underlying mechanisms of their effects on neuronal function remain largely unexplored. In this study, we utilized SH-SY5Y neuroblastoma cells, differentiated into neuronal-like cells, to investigate the impact of six PFAS compounds─perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluorodecanesulfonic acid (PFDS), 8:2 fluorotelomer sulfonate (8:2 FTS), and 8:2 fluorotelomer alcohol (8:2 FTOH)─on neuronal health. Following a 30 μM exposure for 24 h, PFAS accumulation ranged from 40–6500 ng/mg of protein. Transcriptomic analysis revealed 721 differentially expressed genes (DEGs) across treatments (padj < 0.05), with 11 DEGs shared among all PFAS exposures, indicating potential biomarkers for neuronal PFAS toxicity. PFOA-treated cells showed downregulation of genes involved in synaptic growth and neural function, while PFOS, PFDS, 8:2 FTS, and 8:2 FTOH exposures resulted in the upregulation of genes related to hypoxia response and amino acid metabolism. Lipidomic profiling further demonstrated significant increases in fatty acid levels with PFDA, PFDS, and 8:2 FTS and depletion of triacylglycerols with 8:2 FTOH treatments. These findings suggest that the neurotoxic effects of PFAS are structurally dependent, offering insights into the molecular processes that may drive PFAS-induced neuronal dysfunction.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"15 24","pages":"4568–4579 4568–4579"},"PeriodicalIF":4.1,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142843549","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

Lipopolysaccharide Effects on Neurotransmission: Understanding Implications for Depression 脂多糖对神经传递的影响：对抑郁症的理解

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2024-11-27 DOI: 10.1021/acschemneuro.4c0059110.1021/acschemneuro.4c00591

L. Batey, B. Baumberger, H. Khoshbouei and P. Hashemi*,

引用次数: 0

Psychedelics and Entactogens: Call for Papers. 迷幻剂和迷幻药：征集论文。

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2024-11-25 DOI: 10.1021/acschemneuro.4c00773

Craig W Lindsley, Jacob M Hooker, Kelly Chibale, Christa E Müller, Squire J Booker

引用次数: 0

Psychedelics and Entactogens: Call for Papers 迷幻剂和迷幻药：论文征集

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2024-11-25 DOI: 10.1021/acschemneuro.4c0077310.1021/acschemneuro.4c00773

Craig W. Lindsley*, Jacob M. Hooker, Kelly Chibale, Christa E. Müller and Squire J. Booker,

引用次数: 0

A VEGF Fragment Encompassing Residues 10–30 Inhibits Aβ1–42 Amyloid Aggregation and Exhibits Neuroprotective Properties Matching the Full-Length Protein 包含残基10-30的VEGF片段抑制Aβ1 - 42淀粉样蛋白聚集，并显示出与全长蛋白相匹配的神经保护特性

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2024-11-25 DOI: 10.1021/acschemneuro.4c0066910.1021/acschemneuro.4c00669

Stefania Zimbone, M. Laura Giuffrida, Michele F.M. Sciacca, Rita Carrotta, Fabio Librizzi, Danilo Milardi* and Giulia Grasso*,

{"title":"A VEGF Fragment Encompassing Residues 10–30 Inhibits Aβ1–42 Amyloid Aggregation and Exhibits Neuroprotective Properties Matching the Full-Length Protein","authors":"Stefania Zimbone, M. Laura Giuffrida, Michele F.M. Sciacca, Rita Carrotta, Fabio Librizzi, Danilo Milardi* and Giulia Grasso*, ","doi":"10.1021/acschemneuro.4c0066910.1021/acschemneuro.4c00669","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00669https://doi.org/10.1021/acschemneuro.4c00669","url":null,"abstract":"The intricate relationship between brain vascular diseases and neurodegeneration has garnered increased attention in the scientific community. With an aging population, the incidence of these two conditions is likely to increase, making it imperative to understand the underlying common molecular mechanisms and unveiling novel avenues for therapy. Prompted by the observation that Aβ peptide aggregation has been implicated in the development of cerebral amyloid angiopathy (CAA) and that elevated concentrations of vascular endothelial growth factor (VEGF) in the cerebrospinal fluid (CSF) have been correlated with less cognitive decline in Alzheimer’s disease (AD), we demonstrate that a small peptide (Pep9) encompassing the 10–30 sequence of VEGF exhibits significant ability to inhibit the aggregation of the Aβ1–42 peptide, as well as the formation of toxic oligomers. AFM studies confirmed this inhibitory capacity, which is also paralleled by a significant reduction of the random coil to a beta-sheet conformational transition. Further studies have shown that Pep9 protects differentiated neuroblastoma SH-SY5Y cells from Aβ toxicity, being even more effective than full-length protein in preventing amyloid-induced neuronal death. The use of a control peptide wherein two histidines are substituted with glycines (H11G and H12G) suggests a close relationship between the peptide amino acid sequence and its antiaggregating/neuroprotective activity. Overall, this study provides insight into the role of VEGF in AD and suggests that specific VEGF fragments could be beneficial in the treatment of this condition.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"15 24","pages":"4580–4590 4580–4590"},"PeriodicalIF":4.1,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142843957","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

Effect of a SARS-CoV-2 Protein Fragment on the Amyloidogenic Propensity of Human Islet Amyloid Polypeptide SARS-CoV-2蛋白片段对人胰岛淀粉样多肽淀粉样蛋白形成倾向的影响

IF 4.1 3区医学

ACS Chemical Neuroscience Pub Date : 2024-11-24 DOI: 10.1021/acschemneuro.4c0047310.1021/acschemneuro.4c00473

Marvin Bilog, Jennifer Cersosimo, Iliana Vigil, Ruel Z. B. Desamero* and Adam A. Profit*,

{"title":"Effect of a SARS-CoV-2 Protein Fragment on the Amyloidogenic Propensity of Human Islet Amyloid Polypeptide","authors":"Marvin Bilog, Jennifer Cersosimo, Iliana Vigil, Ruel Z. B. Desamero* and Adam A. Profit*, ","doi":"10.1021/acschemneuro.4c0047310.1021/acschemneuro.4c00473","DOIUrl":"https://doi.org/10.1021/acschemneuro.4c00473https://doi.org/10.1021/acschemneuro.4c00473","url":null,"abstract":"Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the onset of COVID-19 have been linked to an increased risk of developing type 2 diabetes. While a variety of mechanisms may ultimately be responsible for the onset of type 2 diabetes under these circumstances, one mechanism that has been postulated involves the increased aggregation of human islet amyloid polypeptide (hIAPP) through direct interaction with SARS-CoV-2 viral proteins. Previous computational studies investigating this possibility revealed that a nine-residue peptide fragment known as SK9 (SFYVYSRVK) from the SARS-CoV-2 envelope protein can stabilize the native conformation of hIAPP1–37 by interacting with the N-terminal region of amylin. One of the areas particularly stabilized through this interaction encompasses residues 15–28 of amylin. Given these findings, we investigated whether SK9 could interact with short amyloidogenic sequences derived from this region of amylin. Here, we employ docking studies, molecular dynamics simulations, and biophysical techniques to provide theoretical as well as direct experimental evidence that SK9 can interact with hIAPP12–18 and hIAPP20–29 peptides. Furthermore, we demonstrate that SK9 not only can interact with these sequences but also serves to prevent the self-assembly of these amyloidogenic peptides. In striking contrast, we also show that SK9 has little effect on the amyloidogenic propensity of full-length amylin. These findings are contrary to previous published simulations involving SK9 and hIAPP1–37. Such observations may assist in clarifying potential mechanisms of the SARS-CoV-2 interaction with hIAPP and its relevance to the onset of type 2 diabetes in the setting of COVID-19.","PeriodicalId":13,"journal":{"name":"ACS Chemical Neuroscience","volume":"15 24","pages":"4431–4440 4431–4440"},"PeriodicalIF":4.1,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acschemneuro.4c00473","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142843710","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