Handbook of experimental pharmacology最新文献_第5页

Locus Coeruleus and Noradrenergic Pharmacology in Neurodegenerative Disease. 神经退行性疾病中的脑室和去甲肾上腺素能药理学。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2023_677

Rachel A Matt, Renee S Martin, Andrew K Evans, Joel R Gever, Gabriel A Vargas, Mehrdad Shamloo, Anthony P Ford

{"title":"Locus Coeruleus and Noradrenergic Pharmacology in Neurodegenerative Disease.","authors":"Rachel A Matt, Renee S Martin, Andrew K Evans, Joel R Gever, Gabriel A Vargas, Mehrdad Shamloo, Anthony P Ford","doi":"10.1007/164_2023_677","DOIUrl":"10.1007/164_2023_677","url":null,"abstract":"Adrenoceptors (ARs) throughout the brain are stimulated by noradrenaline originating mostly from neurons of the locus coeruleus, a brainstem nucleus that is ostensibly the earliest to show detectable pathology in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. The α1-AR, α2-AR, and β-AR subtypes expressed in target brain regions and on a range of cell populations define the physiological responses to noradrenaline, which includes activation of cognitive function in addition to modulation of neurometabolism, cerebral blood flow, and neuroinflammation. As these heterocellular functions are critical for maintaining brain homeostasis and neuronal health, combating the loss of noradrenergic tone from locus coeruleus degeneration may therefore be an effective treatment for both cognitive symptoms and disease modification in neurodegenerative indications. Two pharmacologic approaches are receiving attention in recent clinical studies: preserving noradrenaline levels (e.g., via reuptake inhibition) and direct activation of target adrenoceptors. Here, we review the expression and role of adrenoceptors in the brain, the preclinical studies which demonstrate that adrenergic stimulation can support cognitive function and cerebral health by reversing the effects of noradrenaline depletion, and the human data provided by pharmacoepidemiologic analyses and clinical trials which together identify adrenoceptors as promising targets for the treatment of neurodegenerative disease.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"555-616"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9867049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SLC26 Anion Transporters. SLC26阴离子转运蛋白。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2023_698

Eric R Geertsma, Dominik Oliver

引用次数: 0

New Therapeutic Options in Pulmonal Diseases: Sphingolipids and Modulation of Sphingolipid Metabolism. 肺疾病的新治疗选择：鞘磷脂和鞘磷脂代谢的调节。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2023_700

Burkhard Kleuser, Fabian Schumacher, Erich Gulbins

{"title":"New Therapeutic Options in Pulmonal Diseases: Sphingolipids and Modulation of Sphingolipid Metabolism.","authors":"Burkhard Kleuser, Fabian Schumacher, Erich Gulbins","doi":"10.1007/164_2023_700","DOIUrl":"10.1007/164_2023_700","url":null,"abstract":"Sphingolipids are crucial molecules in the respiratory airways. As in most other tissues and organs, in the lung sphingolipids play an essential role as structural constituents as they regulate barrier function and fluidity of cell membranes. A lung-specific feature is the occurrence of sphingolipids as minor structural components in the surfactant. However, sphingolipids are also key signaling molecules involved in airway cell signaling and their dynamical formation and metabolism are important for normal lung physiology. Dysregulation of sphingolipid metabolism and signaling is involved in altering lung tissue and initiates inflammatory processes promoting the pathogenesis of pulmonal diseases including cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and asthma.In the present review, the important role of specific sphingolipid species in pulmonal diseases will be discussed. Only such an understanding opens up the possibility of developing new therapeutic strategies with the aim of correcting the imbalance in sphingolipid metabolism and signaling. Such delivery strategies have already been studied in animal models of these lung diseases, demonstrating that targeting the sphingolipid profile represents new therapeutic opportunities for lung disorders.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"289-312"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71434218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeted Molecular Therapeutics for Pulmonary Diseases: Addressing the Need for Precise Drug Delivery. 肺部疾病的靶向分子疗法：满足精确给药的需求。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2023_703

Simone Carneiro, Joschka T Müller, Olivia M Merkel

引用次数: 0

Structures of Adrenoceptors. 肾上腺素受体的结构。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2023_674

Lukas Helfinger, Christopher G Tate

{"title":"Structures of Adrenoceptors.","authors":"Lukas Helfinger, Christopher G Tate","doi":"10.1007/164_2023_674","DOIUrl":"10.1007/164_2023_674","url":null,"abstract":"The first structure of an adrenoceptor (AR), the human β2-adrenoceptor (hβ2AR) was published in 2007 and since then a total of 78 structures (up to June 2022) have been determined by X-ray crystallography and electron cryo-microscopy (cryo-EM) of all three βARs (β1, β2 and β3) and four out of six αARs (α1B, α2A, α2B, α2C). The structures are in a number of different conformational states, including the inactive state bound to an antagonist, an intermediate state bound to agonist and active states bound to agonist and an intracellular transducer (G protein or arrestin) or transducer mimetic (nanobody). The structures identify molecular details of how ligands bind in the orthosteric binding pocket (OBP; 19 antagonists, 18 agonists) and also how three different small molecule allosteric modulators bind. The structures have been used to define the molecular details of receptor activation and also the molecular determinants for transducer coupling. This chapter will give a brief overview of the structures, receptor activation, a comparison across the different subfamilies and commonalities of ligand-receptor interactions.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"13-26"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10203494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microneedle and Polymeric Films: Delivery of Proteins, Peptides and Nucleic Acids. 微针和聚合物薄膜：蛋白质、肽和核酸的输送。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2023_653

Yu Wu, Aaron R J Hutton, Anjali Kiran Pandya, Vandana B Patravale, Ryan F Donnelly

{"title":"Microneedle and Polymeric Films: Delivery of Proteins, Peptides and Nucleic Acids.","authors":"Yu Wu, Aaron R J Hutton, Anjali Kiran Pandya, Vandana B Patravale, Ryan F Donnelly","doi":"10.1007/164_2023_653","DOIUrl":"10.1007/164_2023_653","url":null,"abstract":"In the last 20 years, protein, peptide and nucleic acid-based therapies have become the fastest growing sector in the pharmaceutical industry and play a vital role in disease therapy. However, the intrinsic sensitivity and large molecular sizes of biotherapeutics limit the available routes of administration. Currently, the main administration routes of biomacromolecules, such as parenteral, oral, pulmonary, nasal, rectal and buccal routes, each have their limitations. Several non-invasive strategies have been proposed to overcome these challenges. Researchers were particularly interested in microneedles (MNs) and polymeric films because of their less invasiveness, convenience and greater potential to preserve the bioactivity of biotherapeutics. By facilitating with MNs and polymeric films, biomacromolecules could provide significant benefits to patients suffering from various diseases such as cancer, diabetes, infectious and ocular diseases. However, before these devices can be used on patients, how to upscale MN manufacture in a cost-effective and timely manner, as well as the long-term safety of MN and polymeric film applications necessitates further investigation.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"93-111"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9356551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Visualization of Nanocarriers and Drugs in Cells and Tissue. 细胞和组织中纳米载体和药物的可视化。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2023_684

Ulrike Alexiev, Eckart Rühl

引用次数: 0

Nanomedicine - Immune System Interactions: Limitations and Opportunities for the Treatment of Cancer. 纳米医学与免疫系统的相互作用：治疗癌症的局限与机遇。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2023_685

Sara Elsafy, Josbert Metselaar, Twan Lammers

引用次数: 0

Roles of β-adrenoceptor Subtypes and Therapeutics in Human Cardiovascular Disease: Heart Failure, Tachyarrhythmias and Other Cardiovascular Disorders. β肾上腺素受体亚型和治疗药物在人类心血管疾病中的作用：心力衰竭、快速性心律失常和其他心血管疾病。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2024_720

Yee Weng Wong, Haris Haqqani, Peter Molenaar

{"title":"Roles of β-adrenoceptor Subtypes and Therapeutics in Human Cardiovascular Disease: Heart Failure, Tachyarrhythmias and Other Cardiovascular Disorders.","authors":"Yee Weng Wong, Haris Haqqani, Peter Molenaar","doi":"10.1007/164_2024_720","DOIUrl":"10.1007/164_2024_720","url":null,"abstract":"β-Adrenoceptors (β-ARs) provide an important therapeutic target for the treatment of cardiovascular disease. Three β-ARs, β1-AR, β2-AR, β3-AR are localized to the human heart. Activation of β1-AR and β2-ARs increases heart rate, force of contraction (inotropy) and consequently cardiac output to meet physiological demand. However, in disease, chronic over-activation of β1-AR is responsible for the progression of disease (e.g. heart failure) mediated by pathological hypertrophy, adverse remodelling and premature cell death. Furthermore, activation of β1-AR is critical in the pathogenesis of cardiac arrhythmias while activation of β2-AR directly influences blood pressure haemostasis. There is an increasing awareness of the contribution of β2-AR in cardiovascular disease, particularly arrhythmia generation. All β-blockers used therapeutically to treat cardiovascular disease block β1-AR with variable blockade of β2-AR depending on relative affinity for β1-AR vs β2-AR. Since the introduction of β-blockers into clinical practice in 1965, β-blockers with different properties have been trialled, used and evaluated, leading to better understanding of their therapeutic effects and tolerability in various cardiovascular conditions. β-Blockers with the property of intrinsic sympathomimetic activity (ISA), i.e. β-blockers that also activate the receptor, were used in the past for post-treatment of myocardial infarction and had limited use in heart failure. The β-blocker carvedilol continues to intrigue due to numerous properties that differentiate it from other β-blockers and is used successfully in the treatment of heart failure. The discovery of β3-AR in human heart created interest in the role of β3-AR in heart failure but has not resulted in therapeutics at this stage.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"247-295"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adrenoceptors: A Focus on Psychiatric Disorders and Their Treatments. 肾上腺素受体：聚焦精神疾病及其治疗。

Handbook of experimental pharmacology Pub Date : 2024-01-01 DOI: 10.1007/164_2023_675

S Clare Stanford, David J Heal

{"title":"Adrenoceptors: A Focus on Psychiatric Disorders and Their Treatments.","authors":"S Clare Stanford, David J Heal","doi":"10.1007/164_2023_675","DOIUrl":"10.1007/164_2023_675","url":null,"abstract":"Research into the involvement of adrenoceptor subtypes in the cause(s) of psychiatric disorders is particularly challenging. This is partly because of difficulties in developing animal models that recapitulate the human condition but also because no evidence for any causal links has emerged from studies of patients. These, and other obstacles, are outlined in this chapter. Nevertheless, many drugs that are used to treat psychiatric disorders bind to adrenoceptors to some extent. Direct or indirect modulation of the function of specific adrenoceptor subtypes mediates all or part of the therapeutic actions of drugs in various psychiatric disorders. On the other hand, interactions with central or peripheral adrenoceptors can also explain their side effects. This chapter discusses both aspects of the field, focusing on disorders that are prevalent: depression, schizophrenia, anxiety, attention-deficit hyperactivity disorder, binge-eating disorder, and substance use disorder. In so doing, we highlight some unanswered questions that need to be resolved before it will be feasible to explain how changes in the function of any adrenoceptor subtype affect mood and behavior in humans and other animals.","PeriodicalId":12859,"journal":{"name":"Handbook of experimental pharmacology","volume":" ","pages":"507-554"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9876271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0