keyword
https://read.qxmd.com/read/38405714/impaired-26s-proteasome-causes-leaning-and-memory-deficiency-and-induces-neuroinflammation-mediated-by-nf-%C3%AE%C2%BAb-in-mice
#21
Christa C Huber, Eduardo Callegari, Maria Paez, Xiaoping Li, Hongmin Wang
BACKGROUND: Aging and many neurodegenerative disorders, including Alzheimer's disease (AD), show reduced proteasome activity, loss of synapses and increased neuroinflammation in the brain. However, whether proteasome dysfunction causes neuroinflammation remains less understood. METHODS: Here, we studied the effect of impaired 26S proteasome on neuroinflammation in the Psmc1 knockout (KO) mice deficient of a 19S proteasome subunit selectively in the forebrain region...
February 12, 2024: bioRxiv
https://read.qxmd.com/read/38393046/chemical-and-pharmacological-prospection-of-the-ascidian-cystodytes-dellechiajei
#22
JOURNAL ARTICLE
Pedro Jatai Batista, Genoveffa Nuzzo, Carmela Gallo, Dalila Carbone, Mario dell'Isola, Mario Affuso, Giusi Barra, Federica Albiani, Fabio Crocetta, Riccardo Virgili, Valerio Mazzella, Daniela Castiglia, Giuliana d'Ippolito, Emiliano Manzo, Angelo Fontana
Marine invertebrates are a traditional source of natural products with relevant biological properties. Tunicates are soft-bodied, solitary or colonial, sessile organisms that provide compounds unique in their structure and activity. The aim of this work was to investigate the chemical composition of the ascidian Cystodytes dellechiajei , selected on the basis of a positive result in biological screening for ligands of relevant receptors of the innate immune system, including TLR2, TLR4, dectin-1b, and TREM2...
January 31, 2024: Marine Drugs
https://read.qxmd.com/read/38392305/strem2-differentially-affects-cytokine-expression-in-myeloid-derived-cell-models-via-mapk-jnk-signaling-pathway
#23
JOURNAL ARTICLE
Ryan Arsenault, Steven Marshall, Patrick Salois, Qiao Li, Wandong Zhang
TREM2 is a critical innate immune receptor primarily expressed on myeloid-derived cells, such as microglia and macrophages. Mutations in TREM2 are linked to several neurodegenerative diseases including Alzheimer's disease (AD). TREM2 can be cleaved from the cell membrane and released as soluble TREM2 (sTREM2). sTREM2 levels are shown to peak prior to AD, with its levels fluctuating throughout disease progression. However, the mechanism by which sTREM2 may affect innate immune responses is largely uncharacterized...
January 30, 2024: Biology
https://read.qxmd.com/read/38385967/single-cell-rna-seq-reveals-transcriptomic-modulation-of-alzheimer-s-disease-by-activated-protein-c
#24
JOURNAL ARTICLE
Mohammad Kasim Fatmi, Hao Wang, Lily Slotabec, Changhong Wen, Blaise Seale, Bi Zhao, Ji Li
Single-Cell RNA sequencing reveals changes in cell population in Alzheimer's disease (AD) model 5xFAD (5x Familial AD mutation) versus wild type (WT) mice. The returned sequencing data was processed through the 10x Genomics CellRanger platform to perform alignment and form corresponding matrix to perform bioinformatic analysis. Alterations in glial cells occurred in 5xFAD versus WT, especially increases in microglia proliferation were profound in 5xFAD. Differential expression testing of glial cells in 5xFAD versus WT revealed gene regulation...
February 21, 2024: Aging
https://read.qxmd.com/read/38385291/high-dimensional-single-cell-multimodal-landscape-of-human-carotid-atherosclerosis
#25
JOURNAL ARTICLE
Alexander C Bashore, Hanying Yan, Chenyi Xue, Lucie Y Zhu, Eunyoung Kim, Thomas Mawson, Johana Coronel, Allen Chung, Nadja Sachs, Sebastian Ho, Leila S Ross, Michael Kissner, Emmanuelle Passegué, Robert C Bauer, Lars Maegdefessel, Mingyao Li, Muredach P Reilly
BACKGROUND: Atherosclerotic plaques are complex tissues composed of a heterogeneous mixture of cells. However, our understanding of the comprehensive transcriptional and phenotypic landscape of the cells within these lesions is limited. METHODS: To characterize the landscape of human carotid atherosclerosis in greater detail, we combined cellular indexing of transcriptomes and epitopes by sequencing and single-cell RNA sequencing to classify all cell types within lesions (n=21; 13 symptomatic) to achieve a comprehensive multimodal understanding of the cellular identities of atherosclerosis and their association with clinical pathophysiology...
February 22, 2024: Arteriosclerosis, Thrombosis, and Vascular Biology
https://read.qxmd.com/read/38373093/unlocking-therapeutic-potential-computational-insights-into-trem2-protein-targeting-with-fda-approved-drugs-for-neurodegeneration
#26
JOURNAL ARTICLE
Mohammed Alrouji, Sabina Yasmin, Fahad A Alhumaydhi, Sharaf E Sharaf, Moyad Shahwan, Anas Shamsi
Neurodegenerative diseases such as Alzheimer's disease (AD) pose a significant global health challenge that requires the exploration of innovative therapeutic strategies. Triggering receptor expressed on myeloid cells-2 (TREM2) is one of the critical proteins involved in immune regulation and neuroinflammation. It has emerged as a promising therapeutic target to develop treatments for neurodegenerative disorders like AD. Here, we employed a comprehensive virtual screening approach to identify potential small molecule inhibitors among FDA-approved drugs for TREM2...
February 19, 2024: Journal of Biomolecular Structure & Dynamics
https://read.qxmd.com/read/38372949/a-phase-1b-open-label-study-to-evaluate-the-safety-tolerability-pharmacokinetics-and-pharmacodynamics-of-py314-in-combination-with-pembrolizumab-in-patients-with-advanced-renal-cell-carcinoma
#27
JOURNAL ARTICLE
Kathryn E Beckermann, Amita Patnaik, Ira Winer, Winston Tan, Babar Bashir, Christos E Kyriakopoulos, Randy F Sweis, Marc Chamberlain, Brian I Rini
Checkpoint inhibition (CPI) is a standard therapeutic approach in metastatic renal cell carcinoma (RCC). However, not all patients respond to CPI, and the immune suppressive characteristics of the RCC tumor microenvironment may contribute to treatment failure. Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) is a transmembrane protein expressed on a subset of myeloid cells with M2-like anti-inflammatory properties that has previously been associated with disease recurrence after nephrectomy and poor outcomes when expressed at high levels...
February 19, 2024: Investigational New Drugs
https://read.qxmd.com/read/38370418/molecular-and-immunological-features-of-trem1-and-its-emergence-as-a-prognostic-indicator-in-glioma
#28
JOURNAL ARTICLE
Lin Zhang, Xun Qu, Yangyang Xu
Triggering receptor expressed on myeloid cells 1 (TREM1), which belongs to the Ig-like superfamily expressed on myeloid cells, is reportedly involved in various diseases but has rarely been studied in glioma. In this study, the prognostic value and functional roles of TREM2 in glioma were analyzed. TERM1 was observed to be significantly upregulated in GBM compared to in other grade gliomas and was associated with poor prognosis. Increased TREM1 accompanied distinct mutation and amplification of driver oncogenes...
2024: Frontiers in Immunology
https://read.qxmd.com/read/38360943/adipocyte-p53-coordinates-the-response-to-intermittent-fasting-by-regulating-adipose-tissue-immune-cell-landscape
#29
JOURNAL ARTICLE
Isabel Reinisch, Helene Michenthaler, Alba Sulaj, Elisabeth Moyschewitz, Jelena Krstic, Markus Galhuber, Ruonan Xu, Zina Riahi, Tongtong Wang, Nemanja Vujic, Melina Amor, Riccardo Zenezini Chiozzi, Martin Wabitsch, Dagmar Kolb, Anastasia Georgiadi, Lisa Glawitsch, Ellen Heitzer, Tim J Schulz, Michael Schupp, Wenfei Sun, Hua Dong, Adhideb Ghosh, Anne Hoffmann, Dagmar Kratky, Laura C Hinte, Ferdinand von Meyenn, Albert J R Heck, Matthias Blüher, Stephan Herzig, Christian Wolfrum, Andreas Prokesch
In obesity, sustained adipose tissue (AT) inflammation constitutes a cellular memory that limits the effectiveness of weight loss interventions. Yet, the impact of fasting regimens on the regulation of AT immune infiltration is still elusive. Here we show that intermittent fasting (IF) exacerbates the lipid-associated macrophage (LAM) inflammatory phenotype of visceral AT in obese mice. Importantly, this increase in LAM abundance is strongly p53 dependent and partly mediated by p53-driven adipocyte apoptosis...
February 15, 2024: Nature Communications
https://read.qxmd.com/read/38360363/the-reduction-of-microglial-efferocytosis-is-concomitant-with-depressive-like-behavior-in-cums-treated-mice
#30
JOURNAL ARTICLE
Ying Xiao, Yuxiang Chen, Shiqi Huang, Hui He, Nan Hu, Shanyu Lin, Zili You
BACKGROUND: Microglial efferocytosis plays a crucial role in facilitating and sustaining homeostasis in the central nervous system, and it is involved in neuropsychiatric disorders. How microglial efferocytosis is affected under the condition of major depressive disorder (MDD) remains elusive. In this study, we hypothesized that microglial efferocytosis in the hippocampus is impaired in the chronic unpredicted mild stress (CUMS) model of MDD, which is involved in the development of MDD...
February 13, 2024: Journal of Affective Disorders
https://read.qxmd.com/read/38356322/microglial-reactivity-correlates-with-presynaptic-loss-independent-of-%C3%AE-amyloid-and-tau
#31
JOURNAL ARTICLE
Guoyu Lan, Xuhui Chen, Jie Yang, Pan Sun, Yue Cai, Anqi Li, Yalin Zhu, Zhen Liu, Shaohua Ma, Tengfei Guo
OBJECTIVE: Triggering receptor expressed on myeloid cells-2 (TREM2) and progranulin (PGRN) are critical regulators of microglia activation and can be detected in cerebrospinal fluid (CSF). However, whether microglial reactivity is detrimental or neuroprotective for Alzheimer disease (AD) is still debatable. METHODS: We identified 663 participants with baseline β-amyloid (Aβ) positron emission tomography (PET) and CSF biomarker data, including phosphorylated tau181 (p-Tau181 ), soluble TREM2 (sTREM2), PGRN, and growth-associated protein-43 (GAP-43)...
February 14, 2024: Annals of Neurology
https://read.qxmd.com/read/38348765/trem2-gene-induces-differentiation-of-induced-pluripotent-stem-cells-into-dopaminergic-neurons-and-promotes-neuronal-repair-via-tgf-%C3%AE-activation-in-6-ohda-lesioned-mouse-model-of-parkinson-s-disease
#32
JOURNAL ARTICLE
Hanbai Liang, Ping Liu, Zijing Wang, Huan Xiong, Cheng Yin, Dongdong Zhao, Chunhui Wu, Longyi Chen
OBJECTIVE: Induced pluripotent stem cells (iPSCs) hold a promising potential for rescuing dopaminergic neurons in therapy for Parkinson's disease (PD). This study clarifies a TREM2-dependent mechanism explaining the function of iPSC differentiation in neuronal repair of PD. METHODS: PD-related differentially expressed genes were screened by bioinformatics analyses and their expression was verified using RT-qPCR in nigral tissues of 6-OHDA-lesioned mice. Following ectopic expression and depletion experiments in iPSCs, cell differentiation into dopaminergic neurons as well as the expression of dopaminergic neuronal markers TH and DAT was measured...
February 2024: CNS Neuroscience & Therapeutics
https://read.qxmd.com/read/38348659/bodipy-based-analogue-of-the-trem2-binding-molecular-adjuvant-sulfavant-a-a-chemical-tool-for-imaging-and-tracking-biological-systems
#33
JOURNAL ARTICLE
Laura Fioretto, Carmela Gallo, Marcello Mercogliano, Marcello Ziaco, Genoveffa Nuzzo, Giuliana d'Ippolito, Olimpia Follero, Marina DellaGreca, Paolo Giaccio, Valeria Nittoli, Concetta Ambrosino, Paolo Sordino, Alessandro Soluri, Andrea Soluri, Roberto Massari, Marcello D'Amelio, Raffaele De Palma, Angelo Fontana, Emiliano Manzo
Recently, we described synthetic sulfolipids named Sulfavants as a novel class of molecular adjuvants based on the sulfoquinovosyl-diacylglycerol skeleton. The members of this family, Sulfavant A ( 1 ), Sulfavant R ( 2 ), and Sulfavant S ( 3 ), showed important effects on triggering receptor expressed on myeloid cells 2 (TREM2)-induced differentiation and maturation of human dendritic cells (hDC), through a novel cell mechanism underlying the regulation of the immune response. As these molecules are involved in biological TREM2-mediated processes crucial for cell survival, here, we report the synthesis and application of a fluorescent analogue of Sulfavant A bearing the 4,4-difluoro-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza- s -indacene moiety (Me4 -BODIPY)...
February 13, 2024: Analytical Chemistry
https://read.qxmd.com/read/38348100/study-on-pyroptosis-related-genes-casp8-gsdmd-and-trem2-in-mice-with-cerebral-infarction
#34
JOURNAL ARTICLE
Shunli Liang, Linsheng Xu, Xilin Xin, Rongbo Zhang, You Wu
OBJECTIVE: Cerebral infarction is the main cause of death in patients with cerebrovascular diseases. Our research aimed to screen and validate pyroptosis-related genes in cerebral infarction for the targeted therapy of cerebral infarction. METHODS AND RESULTS: A total of 1,517 differentially expressed genes (DEGs) were obtained by DESeq2 software analysis. Gene set enrichment analysis results indicated that genes of middle cerebral artery occlusion (MCAO) mice aged 3 months and 18 months were enriched in pyroptosis, respectively...
2024: PeerJ
https://read.qxmd.com/read/38347225/functional-bri2-trem2-interactions-in-microglia-implications-for-alzheimer-s-and-related-dementias
#35
JOURNAL ARTICLE
Tao Yin, Metin Yesiltepe, Luciano D'Adamio
ITM2B/BRI2 mutations cause Alzheimer's Disease (AD)-related dementias. We observe heightened ITM2B/BRI2 expression in microglia, a pivotal cell type in AD due to risk-increasing variants in the microglial gene TREM2. Single-cell RNA-sequencing demonstrates a Trem2/Bri2-dependent microglia cluster, underscoring their functional interaction. α-secretase cleaves TREM2 into TREM2-CTF and sTREM2. As BRI2 hinders α-secretase cleavage of the AD-related Aβ-Precursor-Protein, we probed whether BRI2 influences TREM2 processing...
February 12, 2024: EMBO Reports
https://read.qxmd.com/read/38343132/gene-replacement-alzheimer-s-disease-gr-ad-modeling-the-genetics-of-human-dementias-in-mice
#36
JOURNAL ARTICLE
Kellie Benzow, Kul Karanjeet, Adrian L Oblak, Gregory W Carter, Michael Sasner, Michael D Koob
INTRODUCTION: Genetic studies conducted over the past four decades have provided us with a detailed catalog of genes that play critical roles in the etiology of Alzheimer's disease (AD) and related dementias (ADRDs). Despite this progress, as a field we have had only limited success in incorporating this rich complexity of human AD/ADRD genetics findings into our animal models of these diseases. Our primary goal for the gene replacement (GR)-AD project is to develop mouse lines that model the genetics of AD/ADRD as closely as possible...
February 11, 2024: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://read.qxmd.com/read/38342422/the-neurotransmitter-puzzle-of-alzheimer-s-dissecting-mechanisms-and-exploring-therapeutic-horizons
#37
REVIEW
Monika Sharma, Pankaj Pal, Sukesh Kumar Gupta
Alzheimer's Disease (AD) represents a complex interplay of neurological pathways and molecular mechanisms, with significant impacts on patients' lives. This review synthesizes the latest developments in AD research, focusing on both the scientific advancements and their clinical implications. We examine the role of microglia in AD, highlighting their contribution to the disease's inflammatory aspects. The cholinergic hypothesis, a cornerstone of AD research, is re-evaluated, including the role of Alpha-7 Nicotinic Acetylcholine Receptors in disease progression...
February 9, 2024: Brain Research
https://read.qxmd.com/read/38328219/alzheimer-s-disease-linked-risk-alleles-elevate-microglial-cgas-associated-senescence-and-neurodegeneration-in-a-tauopathy-model
#38
Gillian K Carling, Li Fan, Nessa R Foxe, Kendra Norman, Pearly Ye, Man Ying Wong, Daphne Zhu, Fangmin Yu, Jielin Xu, Allan Yarahmady, Hao Chen, Yige Huang, Sadaf Amin, Emmanouil Zacharioudakis, Xiaoying Chen, David M Holtzman, Sue-Ann Mok, Evripidis Gavathiotis, Subhash C Sinha, Feixiong Cheng, Wenjie Luo, Shiaoching Gong, Li Gan
The strongest risk factors for Alzheimer's disease (AD) include the χ4 allele of apolipoprotein E (APOE), the R47H variant of triggering receptor expressed on myeloid cells 2 (TREM2), and female sex. Here, we combine APOE4 and TREM2R47H ( R47H ) in female P301S tauopathy mice to identify the pathways activated when AD risk is the strongest, thereby highlighting disease-causing mechanisms. We find that the R47H variant induces neurodegeneration in female APOE4 mice without impacting hippocampal tau load...
January 25, 2024: bioRxiv
https://read.qxmd.com/read/38326398/trem2-mediates-phagocytosis-in-glioblastoma
#39
JOURNAL ARTICLE
Lisa Kiani
No abstract text is available yet for this article.
February 7, 2024: Nature Reviews. Neurology
https://read.qxmd.com/read/38325196/a-natural-small-molecule-aspidosperma-type-alkaloid-hecubine-as-a-new-trem2-activator-for-alleviating-lipopolysaccharide-induced-neuroinflammation-in-vitro-and-in-vivo
#40
JOURNAL ARTICLE
Lin Li, Yu-Lin He, Nan Xu, Xiu-Fen Wang, Bing Song, Ben-Qin Tang, Simon Ming-Yuen Lee
Neuroinflammation and oxidative stress play a crucial role in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease. The triggering receptor expressed on myeloid cells 2 (TREM2), highly expressed by microglia in the central nervous system (CNS), can modulate neuroinflammatory responses. Currently, there are no approved drugs specifically targeting TREM2 for CNS diseases. Aspidosperma alkaloids have shown potential as anti-inflammatory and neuroprotective agents. This study aimed to elucidate the potential therapeutic effect of Hecubine, a natural aspidosperma-type alkaloid, as a TREM2 activator in lipopolysaccharide (LPS)-stimulated neuroinflammation in in vitro and in vivo models...
January 24, 2024: Redox Biology
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