The Amyloid-β Pathway in Alzheimer’s Disease

Molecular Psychiatry, Journal Year: 2021, Volume and Issue: 26(10), P. 5481 - 5503

Published: Aug. 30, 2021

Abstract Breakthroughs in molecular medicine have positioned the amyloid-β (Aβ) pathway at center of Alzheimer’s disease (AD) pathophysiology. While detailed mechanisms and spatial-temporal dynamics leading to synaptic failure, neurodegeneration, clinical onset are still under intense investigation, established biochemical alterations Aβ cycle remain core biological hallmark AD promising targets for development disease-modifying therapies. Here, we systematically review update vast state-of-the-art literature science with evidence from basic research studies human genetic multi-modal biomarker investigations, which supports a crucial role dyshomeostasis pathophysiological dynamics. We discuss highlighting differentiated interaction distinct species other AD-related mechanisms, such as tau-mediated, neuroimmune inflammatory changes, well neurochemical imbalance. Through lens latest multimodal vivo biomarkers AD, this cross-disciplinary examines compelling hypothesis- data-driven rationale Aβ-targeting therapeutic strategies early treatment AD.

Language: Английский

---

M2b macrophage polarization and its roles in diseases

Journal of Leukocyte Biology, Journal Year: 2018, Volume and Issue: 106(2), P. 345 - 358

Published: Dec. 21, 2018

Macrophages play an important role in a wide variety of physiologic and pathologic processes. Plasticity functional polarization are hallmarks macrophages. commonly exist two distinct subsets: classically activated macrophages (M1) alternatively (M2). M2b, subtype M2 macrophages, has attracted increasing attention over the past decade due to its strong immune-regulated anti-inflammatory effects. A stimuli multiple factors modulate M2b macrophage vitro vivo. possess both protective pathogenic roles various diseases. Understanding mechanisms activation modulation their might provide great perspective for design novel therapeutic strategies. The purpose this review is discuss current knowledge polarization, diseases polarization.

Language: Английский

---

Macrophage Polarization in Physiological and Pathological Pregnancy

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: April 15, 2019

The immunology of pregnancy is complex and poorly defined. During the process pregnancy, macrophages secrete many cytokines/chemokines play pivotal roles in maintenance maternal-fetal tolerance. Here, we summarized current knowledge macrophage polarization mechanisms involved physiological or pathological processes, including miscarriage, preeclampsia, preterm birth. Although evidence provides a compelling argument that are important our understanding still rudimentary. Since exhibit functional plasticity, they may be ideal targets for therapeutic manipulation during pregnancy. Additional studies needed to better define functions various subsets both normal

Language: Английский

---

Evaluating the Polarization of Tumor-Associated Macrophages Into M1 and M2 Phenotypes in Human Cancer Tissue: Technicalities and Challenges in Routine Clinical Practice

Frontiers in Oncology, Journal Year: 2020, Volume and Issue: 9

Published: Jan. 24, 2020

Tumor associated macrophages (TAMs) as immune cells reside within the tumor microenvironment have gained much interests, basic science regarding their roles in progression unfolds. Better understanding of polarization into pro-tumoral phenotype to promote growth, angiogenesis, evasion and metastasis has prompted various studies investigate clinical significance a biomarker predictive prognostic value across different cancer types. Yet, methodologies phenomena tissue vary. Nonetheless, quantifying ratio M1 M2 TAMs emerged be prevailing parameter evaluate this for application. This mini-review focuses on recent exploring M1/M2 critically evaluates technicalities challenges routine practice. Immunohistochemistry appears preferred methodology TAM evaluation it is readily available laboratories albeit certain limitations. Recommendations are made standardize quantification better transition practice comparison among populations patients

Language: Английский

---

Macrophage Polarization and Its Role in Liver Disease

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Dec. 14, 2021

Macrophages are important immune cells in innate immunity, and have remarkable heterogeneity polarization. Under pathological conditions, addition to the resident macrophages, other macrophages also recruited diseased tissues, polarize various phenotypes (mainly M1 M2) under stimulation of factors microenvironment, thus playing different roles functions. Liver diseases hepatic changes caused by a variety pathogenic (viruses, alcohol, drugs, etc.), including acute liver injury, viral hepatitis, alcoholic disease, metabolic-associated fatty fibrosis, hepatocellular carcinoma. Recent studies shown that macrophage polarization plays an role initiation development diseases. However, because both pathogenesis complex, mechanism need be further clarified. Therefore, origin mechanisms reviewed first this paper. It is found involves several molecular mechanisms, mainly TLR4/NF-κB, JAK/STATs, TGF-β/Smads, PPARγ, Notch, miRNA signaling pathways. In addition, paper expounds diseases, which aims provide references for research contributing therapeutic strategy ameliorating modulating

Language: Английский

---

Single-cell analysis of human glioma and immune cells identifies S100A4 as an immunotherapy target

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Feb. 9, 2022

Abstract A major rate-limiting step in developing more effective immunotherapies for GBM is our inadequate understanding of the cellular complexity and molecular heterogeneity immune infiltrates gliomas. Here, we report an integrated analysis 201,986 human glioma, immune, other stromal cells at single cell level. In doing so, discover extensive spatial infiltrates. We identify signatures nine distinct myeloid subtypes, which five are independent prognostic indicators glioma patient survival. Furthermore, S100A4 as a regulator suppressive T demonstrate that deleting S100a4 non-cancer sufficient to reprogram landscape significantly improve This study provides insights into spatial, molecular, functional glioma-associated demonstrates utility this dataset discovering therapeutic targets poorly immunogenic cancer.

Language: Английский

---

Macrophage phenotypes in tissue repair and the foreign body response: Implications for biomaterial-based regenerative medicine strategies

Acta Biomaterialia, Journal Year: 2021, Volume and Issue: 133, P. 4 - 16

Published: March 27, 2021

Language: Английский

---

Polarization of Tumor-Associated Macrophages by Nanoparticle-Loaded Escherichia coli Combined with Immunogenic Cell Death for Cancer Immunotherapy

Nano Letters, Journal Year: 2021, Volume and Issue: 21(10), P. 4231 - 4240

Published: May 17, 2021

The tumor immunosuppressive microenvironment greatly limits the efficacy of immunotherapy. Tumor-associated macrophages (TAMs) are most abundant cells in microenvironment, which can inhibit after converting it to an M1-like phenotype. In addition, immunogenic cell death (ICD) increase amount T lymphocytes tumors, activating antineoplastic immunity. Herein, tumor-associated macrophage polarization therapy supplemented with PLGA-DOX (PDOX)-induced ICD is developed for cancer treatment. nanoparticles/bacteria complex (Ec-PR848) fabricated targeting and TAM polarization, PLGA-R848 (PR848) attached surface Escherichia coli (E. coli) MG1655 via electrostatic absorption. toll-like receptor 7/8 (TLR7/8) agonist resiquimod (R848) E. polarize M2 M1 macrophages, while PDOX-induced also impair immunosuppression microenvironment. This strategy shows that combined induced by low-dose chemotherapeutic drugs commendably enhance

Language: Английский

---

M1/M2 macrophages and their overlaps – myth or reality?

Clinical Science, Journal Year: 2023, Volume and Issue: 137(15), P. 1067 - 1093

Published: Aug. 1, 2023

Abstract Macrophages represent heterogeneous cell population with important roles in defence mechanisms and homoeostasis. Tissue macrophages from diverse anatomical locations adopt distinct activation states. M1 M2 are two polarized forms of mononuclear phagocyte vitro differentiation phenotypic patterns functional properties, but vivo, there is a wide range different macrophage phenotypes between depending on the microenvironment natural signals they receive. In human infections, pathogens use strategies to combat these include shaping polarization towards one or another phenotype. infiltrating tumours can affect patient’s prognosis. have been shown promote tumour growth, while provide both tumour-promoting anti-tumour properties. autoimmune diseases, prolonged activation, as well altered function contribute their onset activity. atherosclerotic lesions, expressing profiles detected potential factors affecting occurrence cardiovascular diseases. allergic inflammation, T2 cytokines drive profiles, which airway inflammation remodelling. transplantations seem acute rejection, fibrosis graft. The view pro-inflammatory suppressing seems be an oversimplification because cells exploit very high level plasticity large scale immunophenotypes overlapping this respect, it would more precise describe M1-like M2-like.

Language: Английский

---

Therapeutic Targeting of Hepatic Macrophages for the Treatment of Liver Diseases

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: Dec. 3, 2019

Hepatic macrophages play a central role in maintaining homeostasis the liver, as well initiation and progression of liver diseases. can mainly derive from resident hepatic called Kupffer cells or circulating bone marrow-derived monocytes. are self-renewing typically non-migrating stationed sinusoids contrast to originating regulate by mediating immunity against non-pathogenic blood-borne molecules, while participating coordinated immune responses leading pathogen clearance, leukocyte recruitment antigen presentation lymphocytes present vasculature. Monocyte-derived infiltrate into tissue when metabolic toxic damage instigates likely dispensable for replenishing macrophage population homeostasis. In recent years, different populations have been identified with distinct phenotypes discrete functions, far beyond dogma M1 M2 macrophages. pathogenesis acute chronic failure, fibrosis, non-alcoholic fatty disease, alcoholic viral hepatitis, hepatocellular carcinoma, disease resolution. The understanding diseases provides opportunities development targeted therapeutics respective malignancies. This review will summarize current knowledge macrophages, their origin, critical resolution Furthermore, we provide comprehensive overview therapeutic targeting strategies developed treatment

Language: Английский

---