Handbook of clinical neurology最新文献_第4页

Gut microbiota and epigenetic mechanisms in brain physiology and disorders. 肠道微生物群和脑生理和疾病的表观遗传机制。

Handbook of clinical neurology Pub Date : 2026-01-01 DOI: 10.1016/B978-0-443-19043-8.00019-0

Gerard M Moloney, Gerard Clarke, John F Cryan

{"title":"Gut microbiota and epigenetic mechanisms in brain physiology and disorders.","authors":"Gerard M Moloney, Gerard Clarke, John F Cryan","doi":"10.1016/B978-0-443-19043-8.00019-0","DOIUrl":"https://doi.org/10.1016/B978-0-443-19043-8.00019-0","url":null,"abstract":"The interplay between gut microbiota and epigenetic mechanisms plays a crucial role in brain physiology and disorders, highlighting a novel area of research with significant implications for understanding and treating neurologic conditions. The gut microbiota, the diverse community of microorganisms in the digestive tract, influences brain function and health through the gut-brain axis, a complex communication network linking the gastrointestinal tract and the central nervous system. Epigenetic mechanisms, including DNA methylation, histone modification, and noncoding RNA activity, regulate gene expression without altering the DNA sequence, thus shaping neuronal development and plasticity. Recent studies have elucidated how gut microbiota can modulate these epigenetic processes, affecting neurotransmission, neuroinflammation, and the integrity of the blood-brain barrier. Disruptions in the gut microbiome are associated with various psychiatric disorders, such as autism spectrum disorder or depression, and with neurodegenerative diseases, potentially through epigenetic alterations that affect brain function. Understanding the molecular interactions between gut microbiota and epigenetic regulation offers promising avenues for therapeutic interventions, including dietary modifications, probiotics, and epigenetic drugs. This chapter underscores the significance of gut microbiota and epigenetic mechanisms in brain health and disease, suggesting that targeted manipulation of these factors could lead to novel treatments for neurologic disorders.","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"219 ","pages":"147-167"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193002","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

Epigenetic mechanisms in brain development and in neurodegeneration. 脑发育和神经退行性变的表观遗传机制。

Handbook of clinical neurology Pub Date : 2026-01-01 DOI: 10.1016/B978-0-443-19043-8.00030-X

Yiyi Ma, Kevin W Chen, Philip DE Jager

引用次数: 0

Epigenetics processes involved in schizophrenia and antipsychotic treatment. 参与精神分裂症和抗精神病药物治疗的表观遗传学过程。

Handbook of clinical neurology Pub Date : 2026-01-01 DOI: 10.1016/B978-0-443-19043-8.00024-4

Kavita Malik, Simon J C Davies, Nisha Ravindran, Vincenzo DE Luca

{"title":"Epigenetics processes involved in schizophrenia and antipsychotic treatment.","authors":"Kavita Malik, Simon J C Davies, Nisha Ravindran, Vincenzo DE Luca","doi":"10.1016/B978-0-443-19043-8.00024-4","DOIUrl":"https://doi.org/10.1016/B978-0-443-19043-8.00024-4","url":null,"abstract":"Schizophrenia is a severe psychiatric disorder characterized by abnormalities of thought, behavior, cognition, and affect. Risk factors for schizophrenia include a family history of psychosis, obstetric complications, childhood trauma, urban living, illicit substance use, and social isolation. It has long been concluded that there is a genetic component contributing to the development of schizophrenia; however, research studies in the pregenomic, postgenomic, and multiomics eras failed to illustrate the mechanisms underlying the genetic basis for this complex disease. According to these studies, the genetic variants explain only a portion of the risk, and epigenetic mechanisms may explain the remaining part. Epigenetic processes are changes in how genes function and are expressed without altering the corresponding genetic code. The two most studied epigenetic modifications are DNA methylation and posttranslational histone modifications. These changes may mediate the gene-environment interactions at the molecular level and determine the expression of schizophrenia. Recent studies diverted their attention to examining epigenetic changes and biologic aging as potential biomarkers for identifying individuals at risk for psychosis and poor response to treatment. The main purpose of this chapter is to review the current knowledge of epigenetics in schizophrenia and explore the possibilities of targeting epigenetic mechanisms for treatment in psychotic disorders.","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"219 ","pages":"205-221"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193067","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

Epigenetic mechanisms in stress and the hypothalamic-pituitary-adrenal axis. 应激和下丘脑-垂体-肾上腺轴的表观遗传机制。

Handbook of clinical neurology Pub Date : 2026-01-01 DOI: 10.1016/B978-0-443-19043-8.00018-9

Ian C G Weaver

{"title":"Epigenetic mechanisms in stress and the hypothalamic-pituitary-adrenal axis.","authors":"Ian C G Weaver","doi":"10.1016/B978-0-443-19043-8.00018-9","DOIUrl":"https://doi.org/10.1016/B978-0-443-19043-8.00018-9","url":null,"abstract":"The hypothalamic-pituitary-adrenal (HPA) axis is central to regulating the body's stress response. While HPA axis function enables physiologic and behavioral adaptation to stress, dysregulation of its feedback mechanisms - driven by early-life adversity, chronic stress, trauma, or illness - contributes to the pathophysiology of various physical and neuropsychiatric disorders. Gene expression is controlled by chromatin plasticity, which involves epigenetic mechanisms such as DNA methylation, histone modifications, and noncoding RNA regulation. Animal models demonstrate that early-life stressors, including maternal deprivation or chronic social stress, induce stable epigenetic changes in key genes, primarily through DNA methylation and histone acetylation. These modifications result in persistent alterations in gene expression, affecting HPA regulation and behavioral phenotypes. Human studies confirm similar epigenetic signatures associated with stress-related learning, memory, and neuropsychiatric conditions. Epigenome-wide association studies have identified stress-related DNA methylation and histone modification profiles linked to both resilience and susceptibility to stress-induced pathologies. Emerging research highlights the role of noncoding RNAs and chromatin remodeling in fine-tuning HPA function, revealing the complex interplay between genetic risk and environmental modulation. These findings suggest promising therapeutic avenues, including pharmacologic agents targeting epigenetic modifiers, psychosocial interventions, and dietary strategies aimed at restoring HPA axis equilibrium to mitigate stress-related disorders.","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"219 ","pages":"107-123"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193057","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

The epigenetic mechanisms mediating the long-term impacts of toxicants on brain functions and health. 有毒物质对大脑功能和健康的长期影响的表观遗传机制。

Handbook of clinical neurology Pub Date : 2026-01-01 DOI: 10.1016/B978-0-443-19043-8.00021-9

Jane J Pappas, Rita Khoueiry, Lode Godderis, Zdenko Herceg

{"title":"The epigenetic mechanisms mediating the long-term impacts of toxicants on brain functions and health.","authors":"Jane J Pappas, Rita Khoueiry, Lode Godderis, Zdenko Herceg","doi":"10.1016/B978-0-443-19043-8.00021-9","DOIUrl":"https://doi.org/10.1016/B978-0-443-19043-8.00021-9","url":null,"abstract":"Recent advances in toxicoepigenetics have significantly enhanced our understanding of epigenetic modifications induced by toxicant exposures. This review synthesizes current knowledge regarding epigenetic alterations - primarily DNA methylation, histone acetylation, and miRNA perturbations - associated with common toxicants, including arsenic, lead, methylmercury, formaldehyde, α-hexabromocyclododecane, bisphenol A, and fluoxetine. While substantial evidence derives from rodent models, human studies have made crucial contributions by characterizing toxicant-specific epigenetic signatures, identifying affected genes and pathways, and establishing epigenetic regulation as a critical mediator of biologic responses. This review highlights parallels between toxicant-induced epigenetic changes and those observed in neurologic disorders, particularly focusing on the potential of epigenetic marks as early diagnostic tools for synaptic dysfunction in Alzheimer disease, but also focusing on Huntington disease and Parkinson disease. It relies on evidence ranging from exposures in vitro and in vivo (mainly in rodents) to human exposures. It also highlights parallels between toxicant-induced epigenetic changes and those observed in brain cancers. The findings underscore the therapeutic potential of targeting epigenetic mechanisms to mitigate toxicant-induced neurologic effects. We conclude by proposing a strategic framework for further advancing toxicoepigenetic research, emphasizing the creation of a centralized databank for toxicant-induced brain epigenetic alterations, the development of validated epigenetic bioassays, and the integration of functional neuroimaging. Our proposed comprehensive approach, combining genetics, toxicology, epidemiology, and environmental science, aims to inform and enhance risk assessment protocols and therapeutic interventions.","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"219 ","pages":"449-481"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193072","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

The role of histone modification in epigenetic regulation of gene expression and cell specification. 组蛋白修饰在基因表达和细胞规范的表观遗传调控中的作用。

Handbook of clinical neurology Pub Date : 2026-01-01 DOI: 10.1016/B978-0-443-19043-8.00012-8

Carlo Maria Di Liegro, Gabriella Schiera, Italia Di Liegro

{"title":"The role of histone modification in epigenetic regulation of gene expression and cell specification.","authors":"Carlo Maria Di Liegro, Gabriella Schiera, Italia Di Liegro","doi":"10.1016/B978-0-443-19043-8.00012-8","DOIUrl":"https://doi.org/10.1016/B978-0-443-19043-8.00012-8","url":null,"abstract":"During development and differentiation, each cell of multicellular organisms acquires properties fundamental for its specific functions; this happens in the absence of modifications of the DNA nucleotide sequence, and is thus \"epigenetic\" in nature. The sequential restriction of transcriptional activity to the genes involved in metabolic processes and in cell-specific functions depends on modifications of the structural organization of the DNA-protein complex known as chromatin. Importantly, chromatin structure can change in differentiated cells in response to different stimuli, among which hormonal stimulation, and neurotransmission. The main proteins involved in chromatin structure organization are histones, which can be modified in many ways, and that also exist as isoforms (histone variants), with different structural and functional effects on chromatin. Thanks to sequential epigenetic modifications, cells acquire a memory of their past, stored in their chromatin organization. These processes are even more important in the nervous system, responsible for storing the memory of the entire organism. In this chapter, we will discuss the different types of histone modifications, as well as their effects on chromatin structure and function, with a particular focus on nerve cells as well as on the possible relationships among exercise and diet, and histone modifications.","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"219 ","pages":"35-56"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193039","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

Neurotransmitter abnormalities in primary tic disorders and Tourette syndrome. 原发性抽动障碍和抽动秽语综合征的神经递质异常。

Handbook of clinical neurology Pub Date : 2026-01-01 DOI: 10.1016/B978-0-443-13554-5.00023-7

Yulia Worbe, Benjamin Pasquereau

{"title":"Neurotransmitter abnormalities in primary tic disorders and Tourette syndrome.","authors":"Yulia Worbe, Benjamin Pasquereau","doi":"10.1016/B978-0-443-13554-5.00023-7","DOIUrl":"10.1016/B978-0-443-13554-5.00023-7","url":null,"abstract":"Tourette syndrome (TS) and primary tic disorders are increasingly understood as neurodevelopmental conditions arising from dysfunction within the cortico-basal ganglia-thalamo-cortical circuits, which govern motor, cognitive, and affective processes. This chapter reviews current knowledge on the neurochemical underpinnings of TS, drawing on evidence from neuroimaging studies - notably positron emission tomography - genetics, animal models, and neuropathology. Particular emphasis is placed on the roles of dopamine, serotonin, glutamate and γ-aminobutyric acid (GABA). Dopaminergic hyperactivity, especially involving increased D2 receptor sensitivity in the striatum, has been strongly linked to tic expression. Serotonergic dysfunction, though less consistently defined, may contribute to both tics and common comorbidities such as obsessive-compulsive behaviors, anxiety, and depression. However, the exact nature of serotonin's involvement remains unresolved, complicated by the influence of comorbidities and treatment effects. Additionally, glutamate and GABA, the brain's primary excitatory and inhibitory neurotransmitters, respectively, have emerged as crucial in modulating excitatory/inhibitory balance within the cortico-basal ganglia-thalamo-cortical loops. Glutamatergic hyperactivity and GABAergic deficits may lead to the disinhibition of motor outputs, exacerbating tic symptoms, and interact synergistically with dopaminergic circuits. Taken together, these findings underscore the multifactorial and interconnected nature of neurotransmitter abnormalities in TS. Rather than stemming from a single neurochemical deficit, TS likely arises from a complex interplay between multiple systems - dopaminergic, serotonergic, glutamatergic, GABAergic, and others - converging within dysfunctional brain networks that regulate motor and behavioral control.","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"215 ","pages":"225-237"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112789","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

Epidemiology of Tourette syndrome. 抽动秽语综合征的流行病学。

Handbook of clinical neurology Pub Date : 2026-01-01 DOI: 10.1016/B978-0-443-13554-5.00011-0

Donald L Gilbert

引用次数: 0

Progress of neuroimmunotherapies: Witnessing an impressive success in the treatment of neurologic autoimmunities. 神经免疫疗法的进展：在神经自身免疫治疗方面取得了令人印象深刻的成功。

Handbook of clinical neurology Pub Date : 2026-01-01 DOI: 10.1016/B978-0-323-90887-0.00023-7

Marinos C Dalakas

{"title":"Progress of neuroimmunotherapies: Witnessing an impressive success in the treatment of neurologic autoimmunities.","authors":"Marinos C Dalakas","doi":"10.1016/B978-0-323-90887-0.00023-7","DOIUrl":"10.1016/B978-0-323-90887-0.00023-7","url":null,"abstract":"This introductory chapter describes the evolution of immunotherapies in neurology as witnessed from the late 1970s to early 1980s, when the main therapy for all autoimmune neurologic diseases was only oral and IV steroids, to the present. The growing pains, complexities, challenges, and the very slow pace by which newer immunotherapeutic options were evolving are discussed pointing out that effective new therapies started to evolve many years later in the late 1990s to 2000 with plasmapheresis, IVIg, and β-interferon as the only disease modifying therapy (DMT) for multiple sclerosis. These early therapies were, however, the impetus for a subsequent faster pace of exploring new biologics with both failures and successes that steadily led to the present impressively galloping pace of trials and approvals of various monoclonal antibodies against B cells, cytokines, complement, FcRn, and currently Bruton's Tyrosine Kinase (BTK) inhibitors across the spectrum of all autoimmune neurologic diseases collectively pointing out that neuroimmunotherapy is now a \"living process\" with evolving therapeutic schemes that continuously change the therapeutic algorithm. The epitome of this successfully rapidly evolving pace is highlighted by the CAR-T cell therapies, currently explored in all refractory neuro-autoimmunities, when they were not even on the list when this volume began. The chapter describes this remarkable 40-year progress and evolution on immunotherapies in every autoimmune neurologic disease, addresses what has been learnt from the success and failures in the conducted therapeutic trials or targeted therapies, and highlights the promising future as currently projected in neuroimmunotherapeutics.","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"214 ","pages":"3-7"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959270","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

Role of complement in neurologic autoimmunities: Why need to target complement activation for effective immunotherapy. 补体在神经系统自身免疫中的作用：为什么需要靶向补体激活来进行有效的免疫治疗。

Handbook of clinical neurology Pub Date : 2026-01-01 DOI: 10.1016/B978-0-323-90887-0.00014-6

Marinos C Dalakas, Peter J Späth

{"title":"Role of complement in neurologic autoimmunities: Why need to target complement activation for effective immunotherapy.","authors":"Marinos C Dalakas, Peter J Späth","doi":"10.1016/B978-0-323-90887-0.00014-6","DOIUrl":"10.1016/B978-0-323-90887-0.00014-6","url":null,"abstract":"Complement is an effector of innate and adaptive immunity that consists of a multitasking network of plasma and membrane proteins that protects self. It simultaneously kills pathogens but also helps clearing damaged, diseased, or dying self-cells. The complement's complexity is highlighted by three early activation pathways: the relentless nonspecific activation of C3 on guard and the two recognition pathways, the C1q/classical and the MBL/lectin, all converging in activating C3, the fundamental and also most abundant molecule within the complement pathways. In the center of physiology is the alternative pathway (AP) providing the power through its amplification loop (AL) of C3b generation that boosts abundant C3b deposits on pathogens as well as on self-tissue leading eventually to the membrane attack complex (MAC) formation. In autoimmune and autoinflammatory conditions, a derailed complement function or complement misled by pathologic autoantibodies leads to specific cellular destruction. Further, the AL-generated anaphylatoxin and MAC assembly become a source of local inflammation and tissue damage of host cells triggering, or propagating progression of autoimmune neurologic disorders, justifying why targeting complement is an effective means in suppressing neurologic autoimmunities. The chapter highlights key aspects of complement-targeted immunotherapies pointing out the role of new therapeutic agents in the form of monoclonal antibodies, fusion proteins or peptidomimetics, engineered to inhibit specific complement proteins and intercept the downstream events that trigger autoimmunity and neurologic dysfunction. The efficacy or therapeutic potential of the present or evolving anticomplement biologics in ongoing phase I-III clinical trials is discussed as newly available or emerging promising agents in the treatment of autoimmune neurologic conditions poorly responding to current immunotherapies.","PeriodicalId":12907,"journal":{"name":"Handbook of clinical neurology","volume":"214 ","pages":"65-83"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145959292","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