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Historical Perspectives of Parkinson's Disease: Early Clinical Descriptions and Neurological Therapies. 帕金森病的历史展望：早期临床描述和神经疗法。
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-04-01 DOI: 10.1101/cshperspect.a041642
Christopher G Goetz
{"title":"Historical Perspectives of Parkinson's Disease: Early Clinical Descriptions and Neurological Therapies.","authors":"Christopher G Goetz","doi":"10.1101/cshperspect.a041642","DOIUrl":"10.1101/cshperspect.a041642","url":null,"abstract":"<p><p>Although components of possible Parkinson's disease can be found in earlier documents, the first clear medical description was written in 1817 by James Parkinson. In the mid-1800s, Jean-Martin Charcot was particularly influential in refining and expanding this early description and in disseminating information internationally about Parkinson's disease. He separated the clinical spectrum of Parkinson's disease from multiple sclerosis and other disorders characterized by tremor, and he recognized cases that later would likely be classified among the parkinsonism-plus syndromes. Early treatments of Parkinson's disease were based on empirical observation, and anticholinergic drugs were used as early as the nineteenth century. The discovery of dopaminergic deficits in Parkinson's disease and the synthetic pathway of dopamine led to the first human trials of levodopa. Further historically important anatomical, biochemical, and physiological studies identified additional pharmacological and neurosurgical targets for Parkinson's disease and allow modern clinicians to offer an array of therapies aimed at improving function in this still incurable disease.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
The Chicken or the Egg Dilemma: Understanding the Interplay between the Immune System and the β Cell in Type 1 Diabetes. 鸡还是蛋的两难选择：了解 1 型糖尿病中免疫系统与 β 细胞之间的相互作用。
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-04-01 DOI: 10.1101/cshperspect.a041591
Maria Skjøtt Hansen, Pravil Pokharel, Jon Piganelli, Lori Sussel
{"title":"The Chicken or the Egg Dilemma: Understanding the Interplay between the Immune System and the β Cell in Type 1 Diabetes.","authors":"Maria Skjøtt Hansen, Pravil Pokharel, Jon Piganelli, Lori Sussel","doi":"10.1101/cshperspect.a041591","DOIUrl":"10.1101/cshperspect.a041591","url":null,"abstract":"<p><p>In this review, we explore the complex interplay between the immune system and pancreatic β cells in the context of type 1 diabetes (T1D). While T1D is predominantly considered a T-cell-mediated autoimmune disease, the inability of human leukocyte antigen (HLA)-risk alleles alone to explain disease development suggests a role for β cells in initiating and/or propagating disease. This review delves into the vulnerability of β cells, emphasizing their susceptibility to endoplasmic reticulum (ER) stress and protein modifications, which may give rise to neoantigens. Additionally, we discuss the role of viral infections as contributors to T1D onset, and of genetic factors with dual impacts on the immune system and β cells. A greater understanding of the interplay between environmental triggers, autoimmunity, and the β cell will not only lead to insight as to why the islet β cells are specifically targeted by the immune system in T1D but may also reveal potential novel therapeutic interventions.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Lineage-Selective Dependencies in Pediatric Cancers. 小儿癌症的系谱选择依赖性
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-04-01 DOI: 10.1101/cshperspect.a041573
K Elaine Ritter, Adam D Durbin
{"title":"Lineage-Selective Dependencies in Pediatric Cancers.","authors":"K Elaine Ritter, Adam D Durbin","doi":"10.1101/cshperspect.a041573","DOIUrl":"10.1101/cshperspect.a041573","url":null,"abstract":"<p><p>The quest for effective cancer therapeutics has traditionally centered on targeting mutated or overexpressed oncogenic proteins. However, challenges arise in cancers with low mutational burden or when the mutated oncogene is not conventionally targetable, which are common situations in childhood cancers. This obstacle has sparked large-scale unbiased screens to identify collateral genetic dependencies crucial for cancer cell growth. These screens have revealed promising targets for therapeutic intervention in the form of lineage-selective dependency genes, which may have an expanded therapeutic window compared to pan-lethal dependencies. Many lineage-selective dependencies regulate gene expression and are closely tied to the developmental origins of pediatric tumors. Placing lineage-selective dependencies in a transcriptional network model is helpful for understanding their roles in driving malignant cell behaviors. Here, we discuss the identification of lineage-selective dependencies and how two transcriptional models, core regulatory circuits and gene regulatory networks, can serve as frameworks for understanding their individual and collective actions, particularly in cancers affecting children and young adults.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141161168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Zebrafish Models for Drug Discovery and Therapeutic Validation against Non-Tuberculous Mycobacteria. 用于非结核分枝杆菌药物发现和治疗验证的斑马鱼模型。
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-03-27 DOI: 10.1101/cshperspect.a041832
Matt D Johansen, Claire Hamela, Yi Ding, Laurent Kremer
{"title":"Zebrafish Models for Drug Discovery and Therapeutic Validation against Non-Tuberculous Mycobacteria.","authors":"Matt D Johansen, Claire Hamela, Yi Ding, Laurent Kremer","doi":"10.1101/cshperspect.a041832","DOIUrl":"https://doi.org/10.1101/cshperspect.a041832","url":null,"abstract":"<p><p>The incidence of non-tuberculous mycobacteria (NTM) is increasing globally, often surpassing the incidence of new tuberculosis (TB) cases in developed countries. Most NTM are environmental organisms; however, there are a number of opportunistic and pathogenic species that can cause severe infections in animals and humans. Many NTM are intrinsically resistant to anti-TB therapies and are incredibly difficult to treat, resulting in poor treatment outcomes for these patients. Recent advances in preclinical animal models such as the zebrafish models have led to the discovery of highly active antimicrobial and host-directed therapies (HDTs) targeting NTM infections that can be applied to treat human infections. Here, we summarize recent progress and technological advancements in the discovery and development of antimicrobial drugs and HDTs that have been applied to NTM zebrafish infection models. We highlight the future directions for this increasingly applicable animal model for the discovery of next-generation therapies to treat NTM diseases.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Developmental Oncology: Principles and Therapy of Cancers of Children and Young Adults. 发展肿瘤学：儿童和青少年癌症的原理和治疗。
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-03-17 DOI: 10.1101/cshperspect.a041847
Alex Kentsis, Alejandro Gutierrez
{"title":"Developmental Oncology: Principles and Therapy of Cancers of Children and Young Adults.","authors":"Alex Kentsis, Alejandro Gutierrez","doi":"10.1101/cshperspect.a041847","DOIUrl":"https://doi.org/10.1101/cshperspect.a041847","url":null,"abstract":"<p><p>Children and young adults are affected by a number of different cancers. These are developmental in origin and arise, in particular, in susceptible cell types. Recent advances have led to significant progress in our understanding of the underlying causes and the pathogenetic mechanisms involved. This is informing design of therapeutic approaches that offer new hope for patients.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Threats from the Fungal Kingdom. 来自真菌王国的威胁。
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-03-17 DOI: 10.1101/cshperspect.a041630
Arturo Casadevall
{"title":"Threats from the Fungal Kingdom.","authors":"Arturo Casadevall","doi":"10.1101/cshperspect.a041630","DOIUrl":"https://doi.org/10.1101/cshperspect.a041630","url":null,"abstract":"<p><p>The fungal kingdom includes a large set of species with pathogenic potential for humans, plants, and wildlife. Whereas threats from the fungal kingdom to agriculture are appreciated, the potential of fungi to threaten humans, animals, ecosystems, and infrastructure is often unappreciated. Fungal disease and mold damage often follow natural disasters. The threats from the fungal kingdom are amplified by the relative paucity of countermeasures, which includes few antifungal drugs and fungicides and an increasing prevalence of resistance to both. Anthropomorphic climate change resulting in global warming is expected to increase the likelihood and potential number of threats from the fungal kingdom. Preparation against fungal threats requires continued investments in basic research to understand the unique aspects of fungal metabolism, development of vaccines, investment in new drugs and fungicides, and a careful mapping of the natural world to identify the existing taxonomic diversity and their potential for harm.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Parallels in Canonical Developmental Signaling Pathways between Normal Development and the Tumor Microenvironment. 正常发育和肿瘤微环境之间典型发育信号通路的相似之处。
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-03-17 DOI: 10.1101/cshperspect.a041609
Julia Segal, James Cronk, Brendan Ball, Greta Forbes, Kailey Jackett, Kathy Li, Alondra Martinez Osorno, Emily San Andres Montalvan, Alice Browne, Jessica Lake, Rosandra N Kaplan
{"title":"Parallels in Canonical Developmental Signaling Pathways between Normal Development and the Tumor Microenvironment.","authors":"Julia Segal, James Cronk, Brendan Ball, Greta Forbes, Kailey Jackett, Kathy Li, Alondra Martinez Osorno, Emily San Andres Montalvan, Alice Browne, Jessica Lake, Rosandra N Kaplan","doi":"10.1101/cshperspect.a041609","DOIUrl":"https://doi.org/10.1101/cshperspect.a041609","url":null,"abstract":"<p><p>The tumor microenvironment (TME) is comprised of both cellular and stromal elements and plays an essential role in the growth, survival, and dissemination of malignancies. The TME is an organized program that develops with a growing tumor, using many processes involved in normal tissue development. In multiple solid tumors, developmental pathways are used to recruit immunosuppressive cells, including immunosuppressive monocytes and neutrophils, tumor-associated macrophages, and regulatory T cells to block the antitumor immune response. In addition, stromal cells sustain tumor growth via trophic support, angiogenesis, repair mechanisms, and associated immunosuppression, driven, at least in part, by canonical developmental signaling pathways. The microenvironmental ecosystem shapes tumor progression from its earliest inception by modulating important programs that dictate tumor behavior, necessitating further consideration when studying the developmental origins of malignancy. Here, we review the role of developmental pathways in the formation and modulation of the TME in pediatric and adult solid tumors, including Wnt, Notch, Hippo, Hedgehog, TGF-β, BMP, SOX, and OCT.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Imaging of Disease-Related Networks in Parkinson's Disease. 帕金森病疾病相关网络的影像学研究
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-03-17 DOI: 10.1101/cshperspect.a041841
Yoshikazu Nakano, Martin Niethammer, David Eidelberg
{"title":"Imaging of Disease-Related Networks in Parkinson's Disease.","authors":"Yoshikazu Nakano, Martin Niethammer, David Eidelberg","doi":"10.1101/cshperspect.a041841","DOIUrl":"https://doi.org/10.1101/cshperspect.a041841","url":null,"abstract":"<p><p>Functional neuroimaging techniques are increasingly being used to advance the diagnosis and management of Parkinson's disease (PD). Methods such as [<sup>18</sup>F]-fluorodeoxyglucose positron emission tomography (FDG PET), resting-state functional magnetic resonance imaging (rs-fMRI), arterial spin labeling (ASL) MRI, and single-photon emission computed tomography (SPECT) enable the identification of disease-specific patterns like the PD-related pattern (PDRP) and PD cognition-related pattern (PDCP), which correlate with motor and cognitive symptoms. Network analysis using graph theory further elucidates the alterations in brain connectivity associated with PD, providing insights into disease progression and response to treatment. Moreover, these neuroimaging patterns assist in distinguishing PD from atypical parkinsonian syndromes, enhancing diagnostic accuracy. Understanding the impact of genetic variants like <i>LRRK2</i> and <i>GBA1</i> on functional connectivity highlights the potential for precision medicine in PD. As neuroimaging technologies evolve, their integration into clinical practice will be pivotal in the personalized management of PD, offering improved diagnostic precision and targeted therapeutic interventions.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Advances in Studying Cancer Immunology in Mice. 研究小鼠癌症免疫学的进展。
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-03-03 DOI: 10.1101/cshperspect.a041682
Marcus Bosenberg
{"title":"Advances in Studying Cancer Immunology in Mice.","authors":"Marcus Bosenberg","doi":"10.1101/cshperspect.a041682","DOIUrl":"10.1101/cshperspect.a041682","url":null,"abstract":"<p><p>The recent rise in effective immuno-oncology therapies has increased demand for experimental approaches to model anticancer immunity. A variety of mouse models have been developed and used to study cancer immunology. These include mutagen-induced, genetically engineered, syngeneic, and other models of cancer immunology. These models each have the potential to define mechanistic aspects of anticancer immune responses, identify potential therapeutic targets, and serve as preclinical models for further therapeutic development. Specific benefits and liabilities are characteristic of particular cancer immunology modeling approaches. The optimal choice and utilization of models depends on the cancer immunology scientific question being addressed and can serve to increase mechanistic understanding and development of human immuno-oncology therapies.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Toxin-Induced Animal Models of Parkinson's Disease. 毒素诱导的帕金森病动物模型。
IF 7.8 2区 医学
Cold Spring Harbor perspectives in medicine Pub Date : 2025-03-03 DOI: 10.1101/cshperspect.a041643
Kim Tieu, Said S Salehe, Harry J Brown
{"title":"Toxin-Induced Animal Models of Parkinson's Disease.","authors":"Kim Tieu, Said S Salehe, Harry J Brown","doi":"10.1101/cshperspect.a041643","DOIUrl":"10.1101/cshperspect.a041643","url":null,"abstract":"<p><p>The debilitating motor symptoms of Parkinson's disease (PD) result primarily from the degenerative nigrostriatal dopaminergic pathway. To elucidate pathogenic mechanisms and evaluate therapeutic strategies for PD, numerous animal models have been developed. Understanding the strengths and limitations of these models can significantly impact the choice of model, experimental design, and data interpretation. Herein, we systematically review the literature over the past decade. Some models no longer serve the purpose of PD models. The primary objectives of this review are: First, to assist new investigators in navigating through available animal models and making appropriate selections based on the objective of the study. Emphasis will be placed on common toxin-induced murine models. And second, to provide an overview of basic technical requirements for assessing the nigrostriatal pathway's pathology, structure, and function.</p>","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
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