Abstract:
:Immunotherapeutic approaches are currently the most advanced treatments for Alzheimer's disease (AD). Antibodies against amyloid β-peptide (Aβ) bind to amyloid plaques and induce their clearance by microglia via Fc receptor-mediated phagocytosis. Dysfunctions of microglia may play a pivotal role in AD pathogenesis and could result in reduced efficacy of antibody-mediated Aβ clearance. Recently, heterozygous mutations in the triggering receptor expressed on myeloid cells 2 (TREM2), a microglial gene involved in phagocytosis, were genetically linked to late onset AD Loss of TREM2 reduces the ability of microglia to engulf Aβ. We have now investigated whether loss of TREM2 affects the efficacy of immunotherapeutic approaches. We show that anti-Aβ antibodies stimulate Aβ uptake and amyloid plaque clearance in a dose-dependent manner in the presence or absence of TREM2. However, TREM2-deficient N9 microglial cell lines, macrophages as well as primary microglia showed significantly reduced uptake of antibody-bound Aβ and as a consequence reduced clearance of amyloid plaques. Titration experiments revealed that reduced efficacy of amyloid plaque clearance by Trem2 knockout cells can be compensated by elevating the concentration of therapeutic antibodies.
journal_name
EMBO Mol Medjournal_title
EMBO molecular medicineauthors
Xiang X,Werner G,Bohrmann B,Liesz A,Mazaheri F,Capell A,Feederle R,Knuesel I,Kleinberger G,Haass Cdoi
10.15252/emmm.201606370subject
Has Abstractpub_date
2016-09-01 00:00:00pages
992-1004issue
9eissn
1757-4676issn
1757-4684pii
emmm.201606370journal_volume
8pub_type
杂志文章abstract::The endocrine system is crucial for maintaining whole-body homeostasis. Little is known regarding endocrine hormones secreted by the heart other than atrial/brain natriuretic peptides discovered over 30 years ago. Here, we identify growth differentiation factor 15 (GDF15) as a heart-derived hormone that regulates body...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201707604
更新日期:2017-08-01 00:00:00
abstract::Baricitinib is an oral Janus kinase (JAK)1/JAK2 inhibitor approved for the treatment of rheumatoid arthritis (RA) that was independently predicted, using artificial intelligence (AI) algorithms, to be useful for COVID-19 infection via proposed anti-cytokine effects and as an inhibitor of host cell viral propagation. W...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.202012697
更新日期:2020-08-07 00:00:00
abstract::The first EMBO workshop on Emerging Themes in Infection Biology was held last June in the South of France. It gathered scientists working on various pathogens from viruses and bacteria to larger eukaryotic fungi and parasites. Topics included not only the crosstalk between pathogens and their hosts but also the tools ...
journal_title:EMBO molecular medicine
pub_type:
doi:10.1002/emmm.201000087
更新日期:2010-09-01 00:00:00
abstract::Arteriogenesis-the growth of collateral arterioles-partially compensates for the progressive occlusion of large conductance arteries as it may occur as a consequence of coronary, cerebral or peripheral artery disease. Despite being clinically highly relevant, mechanisms driving this process remain elusive. In this con...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201403864
更新日期:2014-08-01 00:00:00
abstract::Mutations in POLG disrupt mtDNA replication and cause devastating diseases often with neurological phenotypes. Defining disease mechanisms has been hampered by limited access to human tissues, particularly neurons. Using patient cells carrying POLG mutations, we generated iPSCs and then neural stem cells. These neural...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.202012146
更新日期:2020-10-07 00:00:00
abstract::5'AMP-activated kinase (AMPK) constitutes a hub for cellular metabolic and growth control, thus representing an ideal therapeutic target for prostate cancers (PCas) characterized by increased lipogenesis and activation of mTORC1 pathway. However, whether AMPK activation itself is sufficient to block cancer cell growth...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201302734
更新日期:2014-04-01 00:00:00
abstract::Nutrient availability is the major regulator of life and reproduction, and a complex cellular signaling network has evolved to adapt organisms to fasting. These sensor pathways monitor cellular energy metabolism, especially mitochondrial ATP production and NAD(+)/NADH ratio, as major signals for nutritional state. We ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201403943
更新日期:2014-06-01 00:00:00
abstract::Progression to severe disease is a difficult problem in treating coronavirus disease 2019 (COVID-19). The purpose of this study is to explore changes in markers of severe disease in COVID-19 patients. Sixty-nine severe COVID-19 patients were included. Patients with severe disease showed significant lymphocytopenia. El...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.202012421
更新日期:2020-07-07 00:00:00
abstract::Mitochondrial (mt) diseases are multisystem disorders due to mutations in nuclear or mtDNA genes. Among the latter, more than 50% are located in transfer RNA (tRNA) genes and are responsible for a wide range of syndromes, for which no effective treatment is available at present. We show that three human mt aminoacyl-t...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201303198
更新日期:2014-02-01 00:00:00
abstract::Trop-2, a cell surface glycoprotein, contains both extracellular epidermal growth factor-like and thyroglobulin type-1 repeat domains. Low TROP2 expression was observed in lung adenocarcinoma tissues as compared with their normal counterparts. The lack of expression could be due to either the loss of heterozygosity (L...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201200222
更新日期:2012-06-01 00:00:00
abstract::Intellectual disability (ID) is a condition that affects approximately 1% of the population (Maulik et al, 2011). The numbers may differ across nations, owing to different systems and diagnosis entries or lack of such, but usually range between 0.6 and 3% (Stromme & Valvatne, 1998). Persons with ID are a heterogeneous...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.202012899
更新日期:2020-10-07 00:00:00
abstract::Follistatin-like 1 (Fstl1) is a secreted protein that is acutely induced in heart following myocardial infarction (MI). In this study, we investigated cell type-specific regulation of Fstl1 and its function in a murine model of MI Fstl1 was robustly expressed in fibroblasts and myofibroblasts in the infarcted area com...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201506151
更新日期:2016-08-01 00:00:00
abstract::On November 14 last year, the British Guardian published an account from an anonymous whistleblower at Google, accusing the company of misconduct in regard to handling sensitive health data. The whistleblower works for Project Nightingale, an attempt by Google to get into the lucrative US healthcare market, by storing...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.202012053
更新日期:2020-03-06 00:00:00
abstract::Mitochondrial metabolism and the generation of reactive oxygen species (ROS) contribute to the acquisition of DNA mutations and genomic instability in cancer. How genomic instability influences the metabolic capacity of cancer cells is nevertheless poorly understood. Here, we show that homologous recombination-defecti...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201911217
更新日期:2020-06-08 00:00:00
abstract::Retinitis pigmentosa, caused predominantly by mutations in photoreceptor genes, currently lacks comprehensive treatment. We discover that retinal microglia contribute non-cell autonomously to rod photoreceptor degeneration by primary phagocytosis of living rods. Using rd10 mice, we found that the initiation of rod deg...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201505298
更新日期:2015-09-01 00:00:00
abstract::The tumor suppressor gene TP53 is the most frequently mutated gene in cancer. The compound APR-246 (PRIMA-1Met/Eprenetapopt) is converted to methylene quinuclidinone (MQ) that targets mutant p53 protein and perturbs cellular antioxidant balance. APR-246 is currently tested in a phase III clinical trial in myelodysplas...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201910852
更新日期:2020-12-14 00:00:00
abstract::Wnt/β-catenin signalling has been suggested to be active in basal-like breast cancer. However, in highly aggressive metastatic triple-negative breast cancers (TNBC) the role of β-catenin and the underlying mechanism(s) for the aggressiveness of TNBC remain unknown. We illustrate that WNT10B induces transcriptionally a...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201201320
更新日期:2013-02-01 00:00:00
abstract::Heart failure entails the inability of the heart to pump blood to vital organs. One of the main risk factors for heart failure is the development of pathological hypertrophy. In this issue of EMBO Molecular Medicine, Li and coworkers show that NCoR1, a co-repressor of transcription factors, inhibits the transcriptiona...
journal_title:EMBO molecular medicine
pub_type: 评论,杂志文章
doi:10.15252/emmm.201911297
更新日期:2019-11-07 00:00:00
abstract::The majority of human colorectal cancers (CRCs) are initiated by mutations arising in the adenomatous polyposis coli (APC) tumour suppressor gene. However, a new class of non-APC mutated CRCs has been defined that have a serrated histopathology and carry the (V600E)BRAF oncogene. Here we have investigated the pathogen...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201000099
更新日期:2010-11-01 00:00:00
abstract::The cell fate determinant Numb is frequently downregulated in human breast cancers (BCs), resulting in p53 inactivation and an aggressive disease course. In the mouse mammary gland, Numb/p53 downregulation leads to aberrant tissue morphogenesis, expansion of the stem cell compartment, and emergence of cancer stem cell...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201606940
更新日期:2017-05-01 00:00:00
abstract::The angiopoietin (Ang)-Tie pathway has been intensely pursued as candidate second-generation anti-angiogenic target. While much of the translational work has focused on the ligand Ang2, the clinical efficacy of Ang2-targeting drugs is limited and failed to improve patient survival. In turn, the orphan receptor Tie1 re...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201911164
更新日期:2020-06-08 00:00:00
abstract::Sequence variations occurring in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) support an essential function of microglia and innate immunity in the pathogenesis of Alzheimer's disease (AD) and other neurodegenerative disorders. TREM2 matures within the secretory pathway, and its ectod...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201707672
更新日期:2017-10-01 00:00:00
abstract::Genomic data sharing is becoming more important as scientists join forces across borders in biomedical research for the benefit of patients and society. The EU's General Data Protection Regulation (GDPR) helps simplify sharing of such data at the European and international level. However, initial optimism has dried up...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201911421
更新日期:2020-03-06 00:00:00
abstract::Group B streptococci (GBS) are Gram-positive bacteria that cause infections in utero and in newborns. We recently showed that the GBS pigment is hemolytic and increased pigment production promotes bacterial penetration of human placenta. However, mechanisms utilized by the hemolytic pigment to induce host cell lysis a...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201404883
更新日期:2015-04-01 00:00:00
abstract::Glycine transporters (GlyT1 and GlyT2) that regulate levels of brain glycine, an inhibitory neurotransmitter with co-agonist activity for NMDA receptors (NMDARs), have been considered to be important targets for the treatment of brain disorders with suppressed NMDAR function such as schizophrenia. However, it remains ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.202012632
更新日期:2021-01-11 00:00:00
abstract::We survive because we adapted to a world of microorganisms. All our epithelial surfaces participate in keeping up an effective barrier against microbes while not initiating ongoing inflammatory processes and risking collateral damage to the host. Major players in this scenario are antimicrobial peptides (AMPs). Such b...
journal_title:EMBO molecular medicine
pub_type: 杂志文章,评审
doi:10.1002/emmm.201201773
更新日期:2013-10-01 00:00:00
abstract::In the normal quiescent vasculature, only 0.01% of endothelial cells (ECs) are proliferating. However, this proportion increases dramatically following the angiogenic switch during tumor growth or wound healing. Recent evidence suggests that this angiogenic switch is accompanied by a metabolic switch. Here, we show th...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201303016
更新日期:2014-05-01 00:00:00
abstract::Translational read-through-inducing drugs (TRIDs) promote read-through of nonsense mutations, placing them in the spotlight of current gene-based therapeutic research. Here, we compare for the first time the relative efficacies of new-generation aminoglycosides NB30, NB54 and the chemical compound PTC124 on retinal to...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201201438
更新日期:2012-11-01 00:00:00
abstract::The current management of colorectal cancer (CRC) would greatly benefit from non-invasive prognostic biomarkers indicative of clinicopathological tumor characteristics. Here, we employed targeted proteomic profiling of 80 glycoprotein biomarker candidates across plasma samples of a well-annotated patient cohort with c...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201404874
更新日期:2015-09-01 00:00:00
abstract::Conventional maximum-tolerated dose (MTD) chemotherapy relies on periodic, massive cancer cell ablation events followed by treatment-free intermissions, stereotypically resulting in resistance, relapse, and mortality. Furthermore, MTD chemotherapy can promote metastatic dissemination via activation of a transcriptiona...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201911416
更新日期:2020-09-07 00:00:00