检索结果-内蒙古大学图书馆

Genome-wide screen identifies cullin-RING ligase machinery required for lenalidomide-dependent CRL4^CRBN activity

BLOOD 2018年第12期132卷 1293-1303页

作者： Sievers, Quinlan L. Gasser, Jessica A. Cowley, Glenn S. Fischer, Eric S. Ebert, Benjamin L. Broad Inst MIT & Harvard Cambridge MA USA Harvard Med Sch Brigham & Womens Hosp Div Hematol Boston MA USA Harvard Med Sch MD PhD Program Boston MA USA Dana Farber Canc Inst Dept Chem Biol Boston MA 02115 USA Harvard Med Sch Dept Biol Chem & Mol Pharmacol Boston MA USA Dana Farber Canc Inst Dept Med Oncol Boston MA 02115 USA

Lenalidomide mediates the ubiquitination and degradation of Ikaros family zinc finger protein 1 (IKZF1), IKZF3, and casein kinase 1 alpha (CK1 alpha) by facilitating their interaction with cereblon (CRBN), the substrate receptor for the CRL4(CRBN) E3 ubiquitin ligase. Through this mechanism, lenalidomide is a clinically effective treatment of multiple myeloma and myelodysplastic syndrome (mdS) with deletion of chromosome 5q [del(5q) mdS]. To identify the cellular machinery required for lenalidomide-induced CRL4(CRBN) activity, we performed a positive selection, genome-scale clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) screen in a lenalidomide-sensitive myeloma cell line. CRBN was the top-ranking gene, with all CRBN-targeting guide RNAs (gRNAs) ranking as the 6 highest-scoring gRNAs. A counterscreen using an IKZF3 degron reporter to assay lenalidomide-induced protein degradation highlighted regulators of cullin-RING ligase neddylation and 2 E2 ubiquitin-conjugating enzymes as necessary for efficient lenalidomide-induced protein degradation. We demonstrated that loss of UBE2M or members of the constitutive photomorphogenesis 9 (COP9) signalosome results in altered neddylation of cullin 4A and impairs lenalidomide-dependent CRL4(CRBN) activity. Additionally, we established that UBE2D3 and UBE2G1 play distinct roles in substrate ubiquitination by CRL4(CRBN), with UBE2D3 acting to prime targets via monoubiquitination and UBE2G1 functioning to extend polyubiquitin chains with lysine 48 linkages. The validation of UBE2D3 and UBE2G1 highlights the functional capacity of CRISPR-Cas9 screening to identify E2 ubiquitin-conjugating enzyme and E3 ubiquitin ligase complex pairings. More broadly, these findings establish key proteins required for lenalidomide-dependent CRL4(CRBN) function in myeloma and inform potential mechanisms of drug resistance.

关键词： MULTIPLE myeloma ZINC-finger proteins MONOCLONAL gammopathies CASEIN kinase MYELODYSPLASTIC syndromes

来源：评论

学校读者我要写书评

暂无评论

Choroid plexus-CSF-targeted antioxidant therapy protects the brain from toxicity of cancer chemotherapy

引用

NEURON 2022年第20期110卷 3288-+页

作者： Jang, Ahram Petrova, Boryana Cheong, Taek-Chin Zawadzki, Miriam E. Jones, Jill K. Culhane, Andrew J. Shipley, Frederick B. Chiarle, Roberto Wong, Eric T. Kanarek, Naama Lehtinen, Maria K. Boston Childrens Hosp Dept Pathol Boston MA 02115 USA Harvard Med Sch Grad Program Biol & Biomed Sci Boston MA 02115 USA Harvard Med Sch MIT MD PhD Program Harvard Boston MA 02115 USA Harvard Univ Grad Program Biophys Cambridge MA 02138 USA Univ Torino Dept Mol Biotechnol & Hlth Sci I-10126 Turin Italy Beth Israel Deaconess Med Ctr Brain Tumor Ctr Boston MA 02115 USA Beth Israel Deaconess Med Ctr Neurooncol Unit Boston MA 02115 USA

For many cancer patients, chemotherapy produces untreatable life-long neurologic effects termed chemo-therapy-related cognitive impairment (CRCI). We discovered that the chemotherapy methotrexate (MTX) adversely affects oxidative metabolism of non-cancerous choroid plexus (ChP) cells and the cerebrospinal fluid (CSF). We used a ChP-targeted adeno-associated viral (AAV) vector approach in mice to augment CSF levels of the secreted antioxidant SOD3. AAV-SOD3 gene therapy increased oxidative defense capacity of the CSF and prevented MTX-induced lipid peroxidation in the hippocampus. Furthermore, this gene ther-apy prevented anxiety and deficits in short-term learning and memory caused by MTX. MTX-induced oxidative damage to cultured human cortical neurons and analyses of CSF samples from MTX-treated lym-phoma patients demonstrated that MTX diminishes antioxidant capacity of patient CSF. Collectively, our findings motivate the advancement of ChP-and CSF-targeted anti-oxidative prophylactic measures to relieve CRCI.

关键词： methotrexate neurotoxicity chemotherapy-induced cognitive impairment CSF choroid plexus antioxidants oxidative stress CSF metabolomics metabolite profiling SOD3

来源：评论

学校读者我要写书评

暂无评论

Streamlined inactivation, amplification, and Cas13-based detection of SARS-CoV-2

引用

NATURE COMMUNICATIONS 2020年第1期11卷 5921页

作者： Arizti-Sanz, Jon Freije, Catherine A. Stanton, Alexandra C. Petros, Brittany A. Boehm, Chloe K. Siddiqui, Sameed Shaw, Bennett M. Adams, Gordon Kosoko-Thoroddsen, Tinna-Solveig F. Kemball, Molly E. Uwanibe, Jessica N. Ajogbasile, Fehintola V. Eromon, Philomena E. Gross, Robin Wronka, Loni Caviness, Katie Hensley, Lisa E. Bergman, Nicholas H. MacInnis, Bronwyn L. Happi, Christian T. Lemieux, Jacob E. Sabeti, Pardis C. Myhrvold, Cameron Broad Inst Massachusetts Inst Technol MIT & Harva Cambridge MA 02142 USA Harvard MIT Program Hlth Sci & Technol 77 Massachusetts Ave Cambridge MA 02139 USA Harvard Med Sch Program Virol Boston MA 02115 USA Harvard MIT MD PhD Program Boston MA 02139 USA MIT Computat & Syst Biol PhD Program Cambridge MA 02139 USA Massachusetts Gen Hosp Dept Med Div Infect Dis 55 Fruit St Gray 730 Boston MA 02114 USA Redeemers Univ African Ctr Excellence Genom Infect Dis ACEGID Ede Osun State Nigeria Redeemers Univ Coll Nat Sci Dept Biol Sci Ede Osun State Nigeria NIAID Integrated Res Facil Div Clin Res NIH Frederick MD 21702 USA Natl Biodef Anal & Countermeasures Ctr Ft Detrick MD 21702 USA Harvard TH Chan Sch Publ Hlth 677 Huntington Ave Boston MA 02115 USA Harvard Univ Dept Organism & Evolutionary Biol 26 Oxford St Cambridge MA 02138 USA Howard Hughes Med Inst Chevy Chase MD 20815 USA Massachusetts Consortium Pathogen Readiness Boston MA 02115 USA Princeton Univ Dept Mol Biol Princeton NJ 08544 USA

The COVID-19 pandemic has highlighted that new diagnostic technologies are essential for controlling disease transmission. Here, we develop SHINE (Streamlined Highlighting of Infections to Navigate Epidemics), a sensitive and specific diagnostic tool that can detect SARS-CoV-2 RNA from unextracted samples. We identify the optimal conditions to allow RPA-based amplification and Cas13-based detection to occur in a single step, simplifying assay preparation and reducing run-time. We improve HUDSON to rapidly inactivate viruses in nasopharyngeal swabs and saliva in 10min. SHINE's results can be visualized with an in-tube fluorescent readout - reducing contamination risk as amplification reaction tubes remain sealed - and interpreted by a companion smartphone application. We validate SHINE on 50 nasopharyngeal patient samples, demonstrating 90% sensitivity and 100% specificity compared to RT-qPCR with a sample-to-answer time of 50min. SHINE has the potential to be used outside of hospitals and clinical laboratories, greatly enhancing diagnostic capabilities. The COVID-19 pandemic has highlighted the need for user-friendly diagnostic techniques. Here, the authors present SHINE, a streamlined and optimised Cas13-based method with accompanying smartphone app for visual diagnosis.

关键词： Assay systems Infectious-disease diagnostics CRISPR-Cas systems Molecular engineering

来源：评论

学校读者我要写书评

暂无评论

Schizophrenia risk from complex variation of complement component 4

引用

NATURE 2016年第7589期530卷 177-+页

作者： Sekar, Aswin Bialas, Allison R. de Rivera, Heather Davis, Avery Hammond, Timothy R. Kamitaki, Nolan Tooley, Katherine Presumey, Jessy Baum, Matthew Van Doren, Vanessa Genovese, Giulio Rose, Samuel A. Handsaker, Robert E. Daly, Mark J. Carroll, Michael C. Stevens, Beth McCarroll, Steven A. Harvard Univ Sch Med Dept Genet Boston MA 02115 USA Broad Inst MIT & Harvard Stanley Ctr Psychiat Res Cambridge MA 02142 USA Harvard Univ Sch Med MD PhD Program Boston MA 02115 USA Harvard Univ Sch Med Boston Childrens Hosp Dept NeurolFM Kirby Neurobiol Ctr Boston MA 02115 USA Boston Childrens Hosp Program Cellular & Mol Med Boston MA 02115 USA Massachusetts Gen Hosp Analyt & Translat Genet Unit Boston MA 02114 USA

Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. Schizophrenia's strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia.

关键词： Genetics Synaptic development Haplotypes Structural variation

来源：评论

学校读者我要写书评

暂无评论

A transcriptomic taxonomy of mouse brain-wide spinal projecting neurons

引用

NATURE 2023年第7991期624卷 403-414页

作者： Winter, Carla C. Jacobi, Anne Su, Junfeng Chung, Leeyup van Velthoven, Cindy T. J. Yao, Zizhen Lee, Changkyu Zhang, Zicong Yu, Shuguang Gao, Kun Duque Salazar, Geraldine Kegeles, Evgenii Zhang, Yu Tomihiro, Makenzie C. Zhang, Yiming Yang, Zhiyun Zhu, Junjie Tang, Jing Song, Xuan Donahue, Ryan J. Wang, Qing Mcmillen, Delissa Kunst, Michael Wang, Ning Smith, Kimberly A. Romero, Gabriel E. Frank, Michelle M. Krol, Alexandra Kawaguchi, Riki Geschwind, Daniel H. Feng, Guoping Goodrich, Lisa V. Liu, Yuanyuan Tasic, Bosiljka Zeng, Hongkui He, Zhigang Boston Childrens Hosp FM Kirby Neurobiol Ctr Boston MA 02115 USA Harvard Med Sch Dept Neurol Boston MA 02115 USA Harvard Med Sch Dept Ophthalmol Boston MA 02115 USA Harvard Med Sch PhD Program Biol & Biomed Sci Boston MA USA Harvard Med Sch Harvard MIT MD PhD Program Boston MA 02115 USA Allen Inst Brain Sci Seattle WA 98109 USA Univ Calif Los Angeles Semel Inst Neurosci & Human Behav David Geffen Sch Med Los Angeles CA USA Univ Calif Los Angeles David Geffen Sch Med Dept Neurol Program Neurogenet Los Angeles CA USA Harvard Med Sch Dept Neurobiol Boston MA USA MIT McGovern Inst Brain Res Dept Brain & Cognit Sci Cambridge MA USA Natl Inst Dent & Craniofacial Res Somatosensat & Pain Unit Natl Ctr Complementary & Integrat Hlth NIH Bethesda MD USA F Hoffman La Roche AG pRED Basel Switzerland

The brain controls nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from the brain to the spinal cord. However, a comprehensive molecular characterization of brain-wide SPNs is still lacking. Here we transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain1. This taxonomy reveals a three-component organization of SPNs: (1) molecularly homogeneous excitatory SPNs from the cortex, red nucleus and cerebellum with somatotopic spinal terminations suitable for point-to-point communication;(2) heterogeneous populations in the reticular formation with broad spinal termination patterns, suitable for relaying commands related to the activities of the entire spinal cord;and (3) modulatory neurons expressing slow-acting neurotransmitters and/or neuropeptides in the hypothalamus, midbrain and reticular formation for 'gain setting' of brain-spinal signals. In addition, this atlas revealed a LIM homeobox transcription factor code that parcellates the reticulospinal neurons into five molecularly distinct and spatially segregated populations. Finally, we found transcriptional signatures of a subset of SPNs with large soma size and correlated these with fast-firing electrophysiological properties. Together, this study establishes a comprehensive taxonomy of brain-wide SPNs and provides insight into the functional organization of SPNs in mediating brain control of bodily functions. In this study, the authors develop a comprehensive taxonomy of brain-wide SPNs, identifying several novel subsets via their transcriptional signatures.

关键词： Neuroscience Regeneration and repair in the nervous system

来源：评论

学校读者我要写书评

暂无评论

Model-directed generation of artificial CRISPR-Cas13a guide RNA sequences improves nucleic acid detection

引用

NATURE BIOTECHNOLOGY 2024年 1-8页

作者： Mantena, Sreekar Pillai, Priya P. Petros, Brittany A. Welch, Nicole L. Myhrvold, Cameron Sabeti, Pardis C. Metsky, Hayden C. Broad Inst MIT & Harvard Cambridge MA 02142 USA Harvard Univ Dept Stat Cambridge MA USA Harvard Univ Dept Mol & Cellular Biol Cambridge MA USA Harvard Med Sch Div Hlth Sci & Technol Cambridge MA USA MIT Cambridge MA USA Harvard Massachusetts Inst Technol MD PhD Program Boston MA USA Harvard Med Sch Dept Syst Biol Boston MA USA Princeton Univ Dept Mol Biol Princeton NJ USA Princeton Univ Dept Chem & Biol Engn Princeton NJ USA Princeton Univ Omenn Darling Bioengn Inst Princeton NJ USA Princeton Univ Dept Chem Princeton NJ USA Howard Hughes Med Inst Chevy Chase MD 20815 USA Harvard Univ Dept Organism & Evolutionary Biol Cambridge MA 02138 USA Harvard TH Chan Sch Publ Hlth Dept Immunol & Infect Dis Boston MA 02115 USA

CRISPR guide RNA sequences deriving exactly from natural sequences may not perform optimally in every application. Here we implement and evaluate algorithms for designing maximally fit, artificial CRISPR-Cas13a guides with multiple mismatches to natural sequences that are tailored for diagnostic applications. These guides offer more sensitive detection of diverse pathogens and discrimination of pathogen variants compared with guides derived directly from natural sequences and illuminate design principles that broaden Cas13a targeting. Model-directed generative design is applied to CRISPR-Cas13a guide RNAs, outperforming natural sequences.

关键词：

来源：评论

学校读者我要写书评

暂无评论

programmable Inhibition and Detection of RNA Viruses Using Cas13

引用

MOLECULAR CELL 2019年第5期76卷 826-+页

作者： Freije, Catherine A. Myhrvold, Cameron Boehm, Chloe K. Lin, Aaron E. Welch, Nicole L. Carter, Amber Metsky, Hayden C. Luo, Cynthia Y. Abudayyeh, Omar O. Gootenberg, Jonathan S. Yozwiak, Nathan L. Zhang, Feng Sabeti, Pardis C. Massachusetts Inst Technol MIT & Harvard Broad Inst Cambridge MA 02142 USA Harvard Med Sch Div Med Sci PhD Program Virol Boston MA 02115 USA Harvard Univ Dept Organism & Evolutionary Biol Cambridge MA 02138 USA MIT Dept Elect Engn & Comp Sci Cambridge MA 02142 USA MIT McGovern Inst Brain Res 77 Massachusetts Ave Cambridge MA 02139 USA MIT Dept Brain & Cognit Sci E25-618 Cambridge MA 02139 USA MIT Dept Biol Engn 77 Massachusetts Ave Cambridge MA 02139 USA MIT Dept Hlth Sci & Technol 77 Massachusetts Ave Cambridge MA 02139 USA Harvard Med Sch Dept Syst Biol Boston MA 02115 USA Howard Hughes Med Inst HHMI Chevy Chase MD 20815 USA TH Chan Harvard Sch Publ Hlth Dept Immunol & Infect Dis Boston MA 02115 USA

The CRISPR effector Cas13 could be an effective antiviral for single-stranded RNA (ssRNA) viruses because it programmably cleaves RNAs complementary to its CRISPR RNA (crRNA). Here, we computationally identify thousands of potential Cas13 crRNA target sites in hundreds of ssRNA viral species that can potentially infect humans. We experimentally demonstrate Cas13's potent activity against three distinct ssRNA viruses: lymphocytic choriomeningitis virus (LCMV);influenza A virus (IAV);and vesicular stomatitis virus (VSV). Combining this antiviral activity with Cas13-based diagnostics, we develop Cas13-assisted restriction of viral expression and readout (CARVER), an end-to-end platform that uses Cas13 to detect and destroy viral RNA. We further screen hundreds of crRNAs along the LCMV genome to evaluate how conservation and target RNA nucleotide content influence Cas13's antiviral activity. Our results demonstrate that Cas13 can be harnessed to target a wide range of ssRNA viruses and CARVER's potential broad utility for rapid diagnostic and antiviral drug development.

关键词： CRISPR Cas13 RNA interference antiviral RNA viruses influenza virus Arenavirus crRNA design multiplexing Cas13-based detection

来源：评论

学校读者我要写书评

暂无评论

The trajectory of gait development in mice

引用

BRAIN AND BEHAVIOR 2020年第6期10卷 01636-01636页

作者： Akula, Shyam K. McCullough, Katherine B. Weichselbaum, Claire Dougherty, Joseph D. Maloney, Susan E. Washington Univ Sch Med Dept Psychiat Campus Box 8232660 South Euclid Ave St Louis MO 63110 USA Washington Univ Sch Med Dept Genet St Louis MO 63110 USA Harvard Med Sch Harvard MIT MD PhD Program Boston MA 02115 USA Washington Univ Sch Med Intellectual & Dev Disabil Res Ctr St Louis MO 63110 USA

Objective Gait irregularities are prevalent in neurodevelopmental disorders (NDDs). However, there is a paucity of information on gait phenotypes in NDD experimental models. This is in part due to the lack of understanding of the normal developmental trajectory of gait maturation in the mouse. Materials and methods Using the DigiGait system, we have developed a quantitative, standardized, and reproducible assay of developmental gait metrics in commonly used mouse strains that can be added to the battery of mouse model phenotyping. With this assay, we characterized the trajectory of gait in the developing C57BL/6J and FVB/AntJ mouse lines. Results In both lines, a mature stride consisted of 40% swing and 60% stance in the forelimbs, which mirrors the mature human stride. In C57BL/6J mice, developmental trajectories were observed for stance width, paw overlap distance, braking and propulsion time, rate of stance loading, peak paw area, and metrics of intraindividual variability. In FVB/AntJ mice, developmental trajectories were observed for percent shared stance, paw overlap distance, rate of stance loading, and peak paw area, although in different directions than C57 mice. By accounting for the impact of body length on stride measurements, we demonstrate the importance of considering body length when interpreting gait metrics. Conclusion Overall, our results show that aspects of mouse gait development parallel a timeline of normal human gait development, such as the percent of stride that is stance phase and swing phase. This study may be used as a standard reference for developmental gait phenotyping of murine models, such as models of neurodevelopmental disease.

关键词： development DigiGait gait motor function mouse mouse strains

来源：评论

学校读者我要写书评

暂无评论

Identification of an oncogenic RAB protein

引用

SCIENCE 2015年第6257期350卷 211-217页

作者： Wheeler, Douglas B. Zoncu, Roberto Root, David E. Sabatini, David M. Sawyers, Charles L. Mem Sloan Kettering Canc Ctr Human Oncol & Pathogenesis Program New York NY 10065 USA Rockefeller Univ Weill Cornell Sloan Kettering Triinst MD PhD Program New York NY 10021 USA Broad Inst MIT & Harvard Cambridge MA 02142 USA Univ Calif Berkeley Dept Mol & Cell Biol Berkeley CA 94720 USA Whitehead Inst Biomed Res Cambridge MA 02142 USA MIT Dept Biol Cambridge MA 02142 USA MIT David H Koch Inst Integrat Canc Res Cambridge MA 02142 USA Howard Hughes Med Inst Chevy Chase MD 20815 USA

In a short hairpin RNA screen for genes that affect AKT phosphorylation, we identified the RAB35 small guanosine triphosphatase (GTPase)-a protein previously implicated in endomembrane trafficking-as a regulator of the phosphatidylinositol 3'-OH kinase (PI3K) pathway. Depletion of RAB35 suppresses AKT phosphorylation in response to growth factors, whereas expression of a dominant active GTPase-deficient mutant of RAB35 constitutively activates the PI3K/AKT pathway. RAB35 functions downstream of growth factor receptors and upstream of PDK1 and mTORC2 and copurifies with PI3K in immunoprecipitation assays. Two somatic RAB35 mutations found in human tumors generate alleles that constitutively activate PI3K/AKT signaling, suppress apoptosis, and transform cells in a PI3K-dependent manner. Furthermore, oncogenic RAB35 is sufficient to drive platelet-derived growth factor receptor a to LAMP2-positive endomembranes in the absence of ligand, suggesting that there may be latent oncogenic potential in dysregulated endomembrane trafficking.

关键词： Alleles Cell Line, Tumor Gene Deletion Humans Immunoprecipitation Lysosomal-Associated Membrane Protein 2/metabolism Multiprotein Complexes/metabolism Mutation Neoplasms/genetics Neoplasms/metabolism Neoplasms/pathology Oncogene Proteins/genetics Oncogene Proteins/metabolism Phosphatidylinositol 3-Kinases/metabolism Phosphorylation/genetics Protein Transport Protein-Serine-Threonine Kinases/metabolism Proto-Oncogene Proteins c-akt/metabolism rab GTP-Binding Proteins/genetics rab GTP-Binding Proteins/metabolism Receptor, Platelet-Derived Growth Factor alpha/metabolism RNA Interference RNA, Small Interfering/genetics RNA, Small Interfering/genetics TOR Serine-Threonine Kinases/metabolism

来源：评论

学校读者我要写书评

暂无评论

Advancements in Immunity and Dementia Research: Highlights from the 2023 AAIC Advancements: Immunity Conference

引用

ALZHEIMERS & DEMENTIA 2025年第1期21卷 e14291页

作者： Kloske, Courtney M. Mahinrad, Simin Barnum, Christopher J. Batista, Andre F. Bradshaw, Elizabeth M. Butts, Brittany Carrillo, Maria C. Chakrabarty, Paramita Chen, Xiaoying Craft, Suzanne Da Mesquita, Sandro Dabin, Luke C. Devanand, Davangere Duran-Laforet, Violeta Elyaman, Wassim Evans, Elizabeth E. Fitzgerald-Bocarsly, Patricia Foley, Kate E. Harms, Ashley S. Heneka, Michael T. Hong, Soyon Huang, Yu-Wen A. Jackvony, Stephanie Lai, Laijun Guen, Yann Le Lemere, Cynthia A. Liddelow, Shane A. Martin-Pena, Alfonso Orr, Anna G. Quintana, Francisco J. Ramey, Grace D. Rexach, Jessica E. Rizzo, Stacey J. S. Sexton, Claire Tang, Alice S. Torrellas, Jose G. Tsai, Andy P. van Olst, Lynn Walker, Keenan A. Wharton, Whitney Tansey, Malu Gamez Wilcock, Donna M. Alzheimers Assoc 225 N Michigan AveFloor 17 Chicago IL 60601 USA INmune Bio Inc Boca Raton FL USA Harvard Med Sch Brigham & Womens Hosp Ann Romney Ctr Neurol Dis Boston MA USA Columbia Univ Carol & Gene Ludwig Ctr Res Neurodegenerat Dept Neurol Div Translat Neurobiol New York NY USA Emory Univ Atlanta GA USA Univ Florida Dept Neurosci Ctr Translat Res Neurodegenerat Dis Gainesville FL 32610 USA Washington Univ Hope Ctr Neurol Disorders Knight Alzheimers Dis Res Ctr Dept NeurolSch Med St Louis MO USA Wake Forest Univ Alzheimers Dis Res Ctr Bowman Gray Sch Med Winston Salem NC USA Mayo Clin Dept Neurosci Jacksonville FL USA Indiana Univ Sch Med Dept Med & Mol Genet Indianapolis IN USA Indiana Univ Sch Med Stark Neurosci Res Inst Indianapolis IN 46202 USA Columbia Univ Irving Med Ctr New York NY USA Univ Massachusetts Brudnick Neuropsychiat Res Inst Dept Neurobiol Chan Med Sch Worcester MA USA Columbia Univ Dept Neurol Div Translat Neurobiol Irving Med Ctr New York NY USA Columbia Univ Taub Inst Res Alzheimers Dis & Aging Brain Irving Med Ctr New York NY USA Vaccinex Inc Rochester NY USA Rutgers New Jersey Med Sch Newark NJ USA Indiana Univ Stark Neurosci Res Inst Indianapolis IN USA Univ Alabama Birmingham Dept Neurol Birmingham AL USA Univ Luxembourg Luxembourg Ctr Syst Biomed Belval Luxembourg Univ Massachusetts Div Infect Dis & Immunol Med Sch North Worcester MA USA UCL UK Dementia Res Inst Inst Neurol London England Brown Univ Providence RI USA Weill Cornell Med Appel Alzheimers Dis Res Inst Feil Family Brain & Mind Res Inst Neurosci Grad Program New York NY USA Univ Connecticut Storrs CT USA Stanford Univ Dept Neurol & Neurol Sci Palo Alto CA USA Stanford Univ Dept Med Quantitat Sci Unit Sch Med Palo Alto CA USA Brigham & Womens Hosp Ann Romney Ctr Neurol Dis Dept Neurol Boston MA 02115 USA Harvard Med Sch Dept Neurol Boston MA USA NYU Neurosci Inst Dept Neurosci & Physiol & Ophthalmol Grossman Sch Med New

The immune system is a key player in the onset and progression of neurodegenerative disorders. While brain resident immune cell-mediated neuroinflammation and peripheral immune cell (eg, T cell) infiltration into the brain have been shown to significantly contribute to Alzheimer's disease (AD) pathology, the nature and extent of immune responses in the brain in the context of AD and related dementias (ADRD) remain unclear. Furthermore, the roles of the peripheral immune system in driving ADRD pathology remain incompletely elucidated. In March of 2023, the Alzheimer's Association convened the Alzheimer's Association International Conference (AAIC), Advancements: Immunity, to discuss the roles of the immune system in ADRD. A wide range of topics were discussed, such as animal models that replicate human pathology, immune-related biomarkers and clinical trials, and lessons from other fields describing immune responses in neurodegeneration. This manuscript presents highlights from the conference and outlines avenues for future research on the roles of immunity in neurodegenerative disorders.

关键词： Alzheimer's disease immunity inflammation microglia therapeutics

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：