International review of neurobiology最新文献

{"title":"Autoantibodies in myasthenia gravis.","authors":"Miriam L Fichtner, Lillith Horstkorte, Blanca G Sánchez Navarro, Hellen Schmidt, Isobel Cabraal, Patrick J Waters, Maria Isabel Leite","doi":"10.1016/bs.irn.2025.04.024","DOIUrl":"https://doi.org/10.1016/bs.irn.2025.04.024","url":null,"abstract":"<p><p>Autoimmune Myasthenia Gravis (MG) is a disease characterized by fatigable muscle weakness and autoantibodies. It can be divided by the presence of serum autoantibodies into two major categories where Immunoglobulin G (IgG) against either the acetylcholine receptor (AChR), or muscle specific kinase (MuSK) causes fatigable muscle weakness. The clinical relevance of Low-density lipoprotein-receptor related protein-4 IgG (LRP4) is debated. These antibodies disrupt neuromuscular transmission via different mechanisms: AChR antibodies, mostly of IgG1 and IgG3 subclass, can activate complement leading to a simplification of the NMJ architecture, block acetylcholine binding to its receptor to prevent channel opening, and internalize AChR. By contrast, MuSK antibodies, mostly of the IgG4 subclass, impair MuSK-LRP4 interactions, and LRP4 antibodies may interfere with agrin-induced clustering. Once these antibody targets were identified the development of antibody assays began. Patrick and Lindstrom made the landmark discovery that antibodies against soluble AChR caused acute flaccid paralysis in immunized rabbits which kickstarted test development. The first, and until recently, most useful test was the radioimmunoassay (RIA) where AChR radiolabeled with toxin from venomous snakes allowed quantitative measurement of AChR-IgG. Most recently the clustered AChR cell-based assays (CBA) provide a significant improvement in test sensitivity over all other methods. MuSK assays followed a similar but shorter path. The accurate detection of AChR and MuSK antibodies has a crucial role in supporting the clinical diagnosis and management of MG which includes a diverse population of patients with a wide range of clinical manifestations, disease severity and response to standard and new therapies. In this chapter we highlight how distinct target-specific IgG autoantibodies cause neuromuscular transmission defects, and subsequently shape disease manifestations in the different MG antibody subgroups. We review the evolution of diagnostic assays, from early RIA to modern CBA, and addresses interpretative pitfalls, particularly in borderline or \"seronegative\" cases. Finally, the authors address the significance of accurate autoantibody detection in the diagnosis and management of patients with one of the antibody MG subtypes, as well as in patients with other autoimmune conditions and thymic malignancies.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"182 ","pages":"89-119"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661420","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}

{"title":"Cell models for studying myasthenia gravis.","authors":"Yu-Fang Huang, Robyn L K Verpalen, Anna Rostedt Punga, Maartje G Huijbers","doi":"10.1016/bs.irn.2025.04.026","DOIUrl":"https://doi.org/10.1016/bs.irn.2025.04.026","url":null,"abstract":"<p><p>Understanding the pathophysiology of Myasthenia Gravis (MG) and developing effective treatments requires using cell models that replicate key features of the disease, particularly those involved in the autoimmune response and neuromuscular dysfunction. This chapter reviews the various cell-based models used in MG research and those with potential for preclinical MG studies, including muscle cells and co-culture models to form neuromuscular junctions (NMJ). We discuss the strengths and limitations of these models, further outline methods for characterizing these, and provide an outlook on the future refinement and abilities of cell models for advancing MG research.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"182 ","pages":"121-143"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661422","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}

{"title":"Preface.","authors":"Anna Rostedt Punga, Carolina Barnett-Tapia","doi":"10.1016/S0074-7742(25)00091-1","DOIUrl":"https://doi.org/10.1016/S0074-7742(25)00091-1","url":null,"abstract":"","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"182 ","pages":"xv"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661428","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}

{"title":"Clinical pharmacology.","authors":"Severin B Vogt, Matthias E Liechti","doi":"10.1016/bs.irn.2025.02.003","DOIUrl":"10.1016/bs.irn.2025.02.003","url":null,"abstract":"<p><p>To design therapeutic trials and select the most appropriate substance and dose for an indication, a detailed understanding of clinical pharmacology is crucial. In recent years, several studies have explored the human pharmacology of different psychedelics and 3,4-methylendioxymethylamphetamin (MDMA). This chapter summarizes pharmacological characteristics of the serotonergic psychedelics psilocybin, lysergic acid diethylamide (LSD), mescaline, N,N-dimethyltryptamine (DMT), 5-methoxy-DMT (5-MeO-DMT), and MDMA. We summarize their mechanisms of action, pharmacokinetics, pharmacodynamics, metabolism, and safety, with a focus on human data from modern clinical trials. Additionally, we provide recommendations for dosing, dose adjustment, and interactions with other medications. We show that the different serotonergic psychedelics produce overall comparable acute subjective and somatic effects primarily through interactions with 5-HT_2A receptors. However, the exact mechanisms of their potential therapeutic benefits in patients remain to be elucidated. Moreover, classic psychedelics differ substantially in their pharmacokinetics and metabolism, resulting mainly in different durations of action, which may influence their suitability for specific therapeutic uses and indications. In contrast, MDMA has a psychopharmacological profile that is distinct from serotonergic psychedelics, characterized by acute stimulant-like and empathogenic effects. In terms of pharmacokinetic-pharmacodynamic relationships, acute effects of the psychedelics mirror their plasma-concentration-time curves, whereas acute effects of MDMA are shorter-lasting than its presence in the body. Thus, MDMA, but not the psychedelics, exhibits marked acute pharmacological tolerance. A good understanding of the pharmacology of classic psychedelics and MDMA forms the basis for their clinical use and the design of clinical therapeutic trials.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"181 ","pages":"99-148"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337314","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}

{"title":"Molecular brain imaging of psychedelic action.","authors":"Paul Cumming, Klemens Egger, Gitte M Knudsen","doi":"10.1016/bs.irn.2025.02.005","DOIUrl":"10.1016/bs.irn.2025.02.005","url":null,"abstract":"<p><p>Molecular brain imaging by positron emission tomography (PET) and single photon emission computer-tomography (SPECT) entails the mapping of the cerebral distribution of radiopharmaceuticals that track physiological processes such as blood perfusion and glucose metabolism, or the abundance in brain of specific molecular targets such as neuroreceptors. PET and SPECT emerged as useful in vivo research technologies in the 1980s, finding early application in the study of psychostimulant drugs. The past decade has seen growing use of molecular imaging methods in the study of psychedelic action, although the published literature remains comparatively small. The preponderance of publications cited in this review are SPECT studies of cerebral perfusion and PET studies of metabolism and neuroreceptors, the latter mainly focusing on the 5-hydroxytryptamine (serotonin) 5-HT_2A receptors, which are largely responsible for the psychedelic action of classical psychedelic substances. There is some documentation of interactions of psychedelics at dopamine D_2/3receptors in the striatum, but many other plausible molecular targets of psychedelic action await investigation by molecular brain imaging. The emerging role of psychedelics as treatments for neurological and psychiatric disorders calls for a broader and systematic investigation of their effects on brain function.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"181 ","pages":"203-230"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337320","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}

{"title":"The role of microbiome in gut-brain-axis dysbiosis causing depression: From mechanisms to treatment.","authors":"Junqiao Mi, Julia Morys, Marta Nowacka-Chmielewska, Malgorzata Burek","doi":"10.1016/bs.irn.2025.03.006","DOIUrl":"https://doi.org/10.1016/bs.irn.2025.03.006","url":null,"abstract":"<p><p>Gut microbiota not only affects the function of the gastrointestinal tract but also the function of other organs, including the brain. The microbiota-gut-brain axis reflects the constant bidirectional communication between the central nervous system and the gastrointestinal tract. Gut microbiota metabolites can cross brain barriers, the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSF) and influence neuropsychiatric disorders, including depression. In recent years, the communication between the microbiome and brain in depression has been extensively studied in humans and animal models. In this chapter, we summarise the current literature on the role of gut microbiota in depression, focusing in particular on brain barriers and bidirectional gut-brain communication.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"180 ","pages":"189-244"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145106","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}

{"title":"History of psychedelic drug science and molecular pharmacology.","authors":"David E Nichols, Charles D Nichols","doi":"10.1016/bs.irn.2025.02.001","DOIUrl":"10.1016/bs.irn.2025.02.001","url":null,"abstract":"<p><p>Classic psychedelics have been used by various cultures for millennia for healing and religious purposes. The modern era of psychedelic science began with the first empirical experiments by Dr. Arthur Heffter in 1898 to determine just what they are when he discovered the active alkaloid in the peyote cactus responsible for its intoxicating effects and named it mescaline. As with many aspects of society there has been a dramatic and often contentious relationship between 'western' society and psychedelics. In the early to mid-20th century, they were seen as valuable medicines with great potential for healing, and as scientific tools for understanding in the nascent field of neuroscience. As the counterculture of the 1960s embraced psychedelics as elements of youthful protest, governments around the world labeled them as dangerous, with no medical value. That ultimately led to severe legal penalties for their possession and essentially halted any significant scientific advances. No clinical studies were carried out for nearly 20 years, with very few preclinical studies performed by only a handful of researchers. As the political climate changed, clinical trials were once again allowed, culminating in several high profile published studies on the efficacy of psychedelics to treat psychiatric disorders. Around that time a paradigm shift in the acceptance of psychedelics as medicines to benefit society began to occur, spurring the rapid growth of the ecosystem surrounding psychedelics research. This review presents an overview of the last 125 years of psychedelic science, with key events and findings along the way highlighted leading to a greater understanding of their pharmacology, chemistry, and therapeutic potential.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"181 ","pages":"3-43"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337318","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}

{"title":"Blood and digital biomarkers in MG.","authors":"Amol K Bhandage, Jiaxin Chen, Henry J Kaminski, Anna Rostedt Punga","doi":"10.1016/bs.irn.2025.04.030","DOIUrl":"https://doi.org/10.1016/bs.irn.2025.04.030","url":null,"abstract":"<p><p>Biomarkers are measurable indicators to assess physiological processes, disease states, or therapy responses. In myasthenia gravis (MG), biomarkers are critical for diagnosis, monitoring, and treatment optimization. Despite advances in MG diagnostics and therapies, predictive biomarkers to personalize treatment remain underdeveloped. Key diagnostic blood biomarkers include antibodies against acetylcholine receptors (AChR) or muscle-specific tyrosine kinase (MuSK), confirming MG diagnosis and guiding treatment decisions. Prognostic markers, such as microRNAs (e.g., miR-150-5p and miR-30e-5p), show promise in predicting disease progression. Pharmacodynamic biomarkers enhance treatment precision, including CD20+ B cell counts for Rituximab and the CYP3A5 gene for Tacrolimus. Emerging research on metabolites, T and B-cell markers, complement factors, and proteomics may help distinguish MG's autoimmune profile. Digital biomarkers, using wearables and sensors, offer innovative patient monitoring. Future efforts integrating multi-omics and big data could revolutionize biomarker discovery, advancing personalized care and improving outcomes for MG patients.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"182 ","pages":"205-226"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661421","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}

{"title":"Thymic physiology and pathophysiology in Myasthenia Gravis.","authors":"Nadine Dragin, Rozen Le Panse","doi":"10.1016/bs.irn.2025.04.023","DOIUrl":"https://doi.org/10.1016/bs.irn.2025.04.023","url":null,"abstract":"<p><p>The thymus is a central lymphoid organ responsible for T-cell development and maturation and is crucial in adaptive immunity. This organ creates a specialized environment for thymocyte differentiation and positive/negative selection, ensuring the survival of functional and self-tolerant T cells while eliminating autoreactive clones. This process, which is known as T-cell education, involves interactions between developing T cells and stromal cells, primarily thymic epithelial cells, which present tissue-specific antigens. Proper thymus function remains vital for maintaining immune homeostasis. However, thymic abnormalities have been implicated in Myasthenia Gravis (MG), where the thymus often exhibits lymphofollicular hyperplasia or thymomas, which may trigger an autoimmune response against the acetylcholine receptor at the neuromuscular junction. This leads to impaired neuromuscular transmission and characteristic muscle weakness. Understanding the etiological mechanisms underlying thymic alterations associated with MG is crucial for elucidating immune dysregulation resulting from an abnormal thymus, which may persist even post-therapeutic thymectomy.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"182 ","pages":"67-88"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661431","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}

{"title":"Preface.","authors":"David John Nutt, Hannah Thurgur","doi":"10.1016/S0074-7742(25)00072-8","DOIUrl":"10.1016/S0074-7742(25)00072-8","url":null,"abstract":"","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"181 ","pages":"xvii"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337323","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}