Cold Spring Harbor perspectives in medicine最新文献_第8页

Genetics of Parkinson's Disease: From Causes to Treatment 帕金森病的遗传学：从病因到治疗

IF 5.4 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-08-12 DOI: 10.1101/cshperspect.a041774

Ana Westenberger, Norbert Brüggemann, Christine Klein

{"title":"Genetics of Parkinson's Disease: From Causes to Treatment","authors":"Ana Westenberger, Norbert Brüggemann, Christine Klein","doi":"10.1101/cshperspect.a041774","DOIUrl":"https://doi.org/10.1101/cshperspect.a041774","url":null,"abstract":"The genetic architecture of Parkinson's disease (PD) comprises five autosomal dominantly inherited forms with a clinical picture overall resembling idiopathic disease (PARK-SNCA, PARK-LRRK2, PARK-VPS35, PARK-CHCHD2, and PARK-RAB32) and three recessive types (PARK-PRKN, PARK-PINK1, and PARK-PARK7), several monogenic forms causing atypical parkinsonism, as well as a plethora of known genetic risk factors, most notably SNCA and GBA1 including a recently discovered risk variant unique to individuals of African descent, as well as polygenic scores. The Movement Disorder Society Genetic mutation database (MDSGene) (www.mdsgene.org) provides PD genotype–phenotype relationships, whereas global PD genetics networks, such as the Global Parkinson's Genetics Program (www.gp2.org) elucidate PD genetic factors at an unprecedented scale. Two large studies in relatively unselected, multicenter PD samples estimate the frequency of genetic forms, including PARK-GBA1, at ∼15%. PD genetics are becoming increasingly actionable, with the first gene-targeted clinical trials underway. Furthermore, PD genetics has recently been incorporated into a new biological classification of PD.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"1 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141934986","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

The Role of B Lymphocytes in Type 1 Diabetes B 淋巴细胞在 1 型糖尿病中的作用

IF 5.4 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-08-12 DOI: 10.1101/cshperspect.a041593

Mia J. Smith, Joanne Boldison, F. Susan Wong

引用次数: 0

Mouse Models of Metastasis and Dormancy. 小鼠转移和休眠模型。

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-08-01 DOI: 10.1101/cshperspect.a041386

Ahmed Mahmoud, Karuna Ganesh

{"title":"Mouse Models of Metastasis and Dormancy.","authors":"Ahmed Mahmoud, Karuna Ganesh","doi":"10.1101/cshperspect.a041386","DOIUrl":"10.1101/cshperspect.a041386","url":null,"abstract":"Metastasis is the ultimate and often lethal stage of cancer. Metastasis occurs in three phases that may vary across individuals: First, dissemination from the primary tumor. Second, tumor dormancy at the metastatic site where micrometastatic cancer cells remain quiescent or, in dynamic cycles of proliferation and elimination, remaining clinically undetectable. Finally, cancer cells are able to overcome microenvironmental constraints for outgrowth, or the formation of clinically detectable macrometastases that colonize distant organs and are largely incurable. A variety of approaches have been used to model metastasis to elucidate molecular mechanisms and identify putative therapeutic targets. In particular, metastatic dormancy has been challenging to model in vivo due to the sparse numbers of cancer cells in micrometastasis nodules and the long latency times required for tumor outgrowth. Here, we review state-of-the art genetically engineered mouse, syngeneic, and patient-derived xenograft approaches for modeling metastasis and dormancy. We describe the advantages and limitations of various metastasis models, novel findings enabled by such approaches, and highlight opportunities for future improvement.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10925556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10213389","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

Germline Genetic Testing for Hereditary Breast and Ovarian Cancer: Current Concepts in Risk Evaluation. 遗传性乳腺癌和卵巢癌的基因检测：风险评估的当前概念》。

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-08-01 DOI: 10.1101/cshperspect.a041318

Siddhartha Yadav, Fergus J Couch, Susan M Domchek

引用次数: 0

Resistance and Resilience to Alzheimer's Disease. 对阿尔茨海默病的抵抗力和复原力。

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-08-01 DOI: 10.1101/cshperspect.a041201

Caitlin S Latimer, Katherine E Prater, Nadia Postupna, C Dirk Keene

{"title":"Resistance and Resilience to Alzheimer's Disease.","authors":"Caitlin S Latimer, Katherine E Prater, Nadia Postupna, C Dirk Keene","doi":"10.1101/cshperspect.a041201","DOIUrl":"10.1101/cshperspect.a041201","url":null,"abstract":"Dementia is a significant public health crisis; the most common underlying cause of age-related cognitive decline and dementia is Alzheimer's disease neuropathologic change (ADNC). As such, there is an urgent need to identify novel therapeutic targets for the treatment and prevention of the underlying pathologic processes that contribute to the development of AD dementia. Although age is the top risk factor for dementia in general and AD specifically, these are not inevitable consequences of advanced age. Some individuals are able to live to advanced age without accumulating significant pathology (resistance to ADNC), whereas others are able to maintain cognitive function despite the presence of significant pathology (resilience to ADNC). Understanding mechanisms of resistance and resilience will inform therapeutic strategies to promote these processes to prevent or delay AD dementia. This article will highlight what is currently known about resistance and resilience to AD, including our current understanding of possible underlying mechanisms that may lead to candidate preventive and treatment interventions for this devastating neurodegenerative disease.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":" ","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139048375","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

Optogenetic Vision Restoration. 光遗传学视力恢复。

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-08-01 DOI: 10.1101/cshperspect.a041660

Volker Busskamp, Botond Roska, Jose-Alain Sahel

引用次数: 0

Innate Immunity in Type 1 Diabetes. 1 型糖尿病的先天免疫。

IF 7.8 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-07-29 DOI: 10.1101/cshperspect.a041595

Léo Bertrand, Alexander V Chervonsky, Agnès Lehuen

引用次数: 0

Checkpoint Inhibitor-Induced Autoimmune Diabetes: An Autoinflammatory Disease 检查点抑制剂诱发的自身免疫性糖尿病：一种自身炎症性疾病

IF 5.4 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-07-22 DOI: 10.1101/cshperspect.a041603

Zoe Quandt, Ana Perdigoto, Mark S. Anderson, Kevan C. Herold

引用次数: 0

Inflammatory β-Cell Stress and Immune Surveillance in Type 1 Diabetes 1 型糖尿病的炎性 β 细胞应激和免疫监视

IF 5.4 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-07-22 DOI: 10.1101/cshperspect.a041605

Anil Bhushan, Peter J. Thompson

{"title":"Inflammatory β-Cell Stress and Immune Surveillance in Type 1 Diabetes","authors":"Anil Bhushan, Peter J. Thompson","doi":"10.1101/cshperspect.a041605","DOIUrl":"https://doi.org/10.1101/cshperspect.a041605","url":null,"abstract":"Recent years have seen increased recognition for the role of β-cell stress as a contributing factor to the autoimmune destruction process that ultimately results in symptomatic type 1 diabetes (T1D). Preclinical studies have discovered a variety of stress responses in the β-cell that occur at presymptomatic stages and contribute to disease progression, but unifying explanations of how these mechanisms operate to promote disease progression remain incomplete. We propose that stressed β-cells transition into β-cells expressing inflammatory molecules that provoke an immune response to restore homeostasis by coordinating islet repair and the removal of stressed cells. However, when immune surveillance fails, stressed β-cells accumulate and contribute to autoimmunity. Therapies directed toward stressed β-cells to either curb their inflammatory signaling or to eliminate them (essentially doing the job of the failed immune surveillance) are moving from animal models into the clinic with promising initial results, although the understanding of how the immune response is coordinated by stressed β-cells is not clear. In this article, we discuss β-cell stress responses implicated in T1D pathogenesis based on evidence from humans and highlight existing knowledge gaps in their mechanisms. Future work in this field is poised to target T1D by simultaneously targeting stressed β-cells and the failed immune response to halt the progression of autoimmunity and prevent β-cell destruction.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"45 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141744937","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

Cross Talk between β Cells and Immune Cells: What We Know, What We Think We Know, and What We Should Learn β细胞与免疫细胞之间的交叉对话：我们知道什么、我们认为我们知道什么以及我们应该了解什么

IF 5.4 2区医学

Cold Spring Harbor perspectives in medicine Pub Date : 2024-07-22 DOI: 10.1101/cshperspect.a041604

Fatoumata Samassa, Capucine Holtzmann, Roberto Mallone

{"title":"Cross Talk between β Cells and Immune Cells: What We Know, What We Think We Know, and What We Should Learn","authors":"Fatoumata Samassa, Capucine Holtzmann, Roberto Mallone","doi":"10.1101/cshperspect.a041604","DOIUrl":"https://doi.org/10.1101/cshperspect.a041604","url":null,"abstract":"Type 1 diabetes (T1D) is a disease whose pathogenesis is driven by both immune dysregulation and β-cell dysfunction. While the specialized structure and function of β cells make them vulnerable to autoimmunity, several surface receptor/ligand pairs underlie the cross talk engaged with T lymphocytes and other immune subsets. The expression of these ligands on β cells is coordinately up-regulated by the exposure to interferons, notably the type I interferons that represent the signature cytokines since the early preclinical stages of T1D. Yet, their interaction with receptors expressed on T lymphocytes can favor either β-cell vulnerability or protection. Despite several knowledge gaps, this novel holistic view of autoimmunity that incorporates both immune and β-cell-derived pathogenic drivers is starting to translate into novel therapeutic strategies aimed at decreasing vulnerability and/or increasing these protective mechanisms. This review summarizes the current knowledge in this evolving field, the assumptions that are often taken for granted but lack formal evidence, and the blind spots in this landscape that may hide further therapeutic opportunities.","PeriodicalId":10452,"journal":{"name":"Cold Spring Harbor perspectives in medicine","volume":"20 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141744936","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