The Alzheimers Disease Risk Genes MS4A4A And MS4A6A Cooperate to Negatively Regulate Trem2 and Microglia states DOI Creative Commons

Dalya R. Soond,

Jessica D. Sun,

Angie Yee

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 24, 2024

Genetic variations in MS4A4A and MS4A6A are linked to the regulation of cerebrospinal fluid soluble TREM2 (sTREM2) levels associated with Alzheimer's disease (AD) risk progression. Using CRISPR knockout MS4A4A-degrading antibodies primary human microglia, non-human primates (NHP), a xenotransplantation model amyloid pathology, we provide evidence that negative regulators both transmembrane proteins. They also negatively regulate microglia proliferation, survival, metabolism, lysosomal function, energetics, phagocytosis, disease-fighting states. Mechanistically, find exerts by interacting protecting it from degradation. turn forms complex blocks co-receptor DAP12, which is required for stability, cell surface localization, signaling other receptors. Taken together, data indicate cooperating, post-transcriptional microglial potential drug targets AD.

Язык: Английский

Advancements in 3D models for studying human iPSC-microglia: Insights into neurodevelopment and neurological disorders DOI Creative Commons
Satish Kumar Tiwari, Florent Ginhoux

hLife, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Neurobiological perturbations in bipolar disorder compared to schizophrenia – evidence from cell cultures and brain organoids DOI Creative Commons
Ibrahim A. Akkouh, Jordi Requena Osete, Attila Szabó

и другие.

Biological Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Electrochemical Aptasensor Based on Topological Material Bi2Se3 Sheets for Sensitive Detection of Interferon-γ DOI

X. H. Li,

Jiangyue Bai,

Liang Lin

и другие.

ACS Applied Bio Materials, Год журнала: 2025, Номер unknown

Опубликована: Апрель 7, 2025

Interferon-gamma (IFN-γ), an essential inflammatory cytokine, is intricately associated with a variety of fatal diseases as key early biomarker. In this work, we designed and constructed electrochemical aptasensor based on topological insulator Bi2Se3 sheets. Micron-scale sheets were prepared by exfoliation from single crystals to make electrodes the aptasensors. The unique robust Dirac surface states could enhance charge transfer efficiency solid-liquid interface, improving performance developed exhibits linear response IFN-γ concentration in range 1-100 pg/mL detection limit low 0.6 pg/mL, enabling it meet clinical requirements. aptasensors also shows excellent stability selectivity. Furthermore, was applied human serum comparable standard enzyme-linked immunosorbent assay technique. Our work indicates that has great potential for application other possible biomarkers.

Язык: Английский

Процитировано

0
Physiological roles of embryonic microglia and their perturbation by maternal inflammation DOI Creative Commons
Tatsuro Shimamura,

Masashi Kitashiba,

Kayo Nishizawa

и другие.

Frontiers in Cellular Neuroscience, Год журнала: 2025, Номер 19

Опубликована: Апрель 7, 2025

The interplay between the nervous and immune systems is well documented in context of adult physiology disease. Recent advances understanding cell development have highlighted a significant interaction neural lineage cells microglia, resident brain macrophages, during developmental stages. Throughout development, particularly from embryonic to postnatal stages, diverse are sequentially generated, undergo fate determination, migrate dynamically their appropriate locations while maturing, establish connections with surroundings form circuits. Previous studies demonstrated that microglia contribute this highly orchestrated process, ensuring proper organization structure. These findings underscore need further investigate how behave function within broader framework neurodevelopment. Importantly, recent epidemiological suggested maternal activation (MIA), triggered by various factors, such as viral or bacterial infections, environmental stressors, other external influences, can affect neurogenesis circuit formation, increasing risk neurodevelopmental disorders (NDDs) offspring. Notably, many revealed fetal changes response MIA. Given essential roles vascular inappropriate disruption microglial may impair these critical processes, potentially leading abnormal This review highlights rodent models human shed light on behaviors multifaceted particular focus stage. Furthermore, drawing insights MIA models, explores disrupts disturbances ultimately contributing onset NDDs.

Язык: Английский

Процитировано

0
The Alzheimers Disease Risk Genes MS4A4A And MS4A6A Cooperate to Negatively Regulate Trem2 and Microglia states DOI Creative Commons

Dalya R. Soond,

Jessica D. Sun,

Angie Yee

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 24, 2024

Genetic variations in MS4A4A and MS4A6A are linked to the regulation of cerebrospinal fluid soluble TREM2 (sTREM2) levels associated with Alzheimer's disease (AD) risk progression. Using CRISPR knockout MS4A4A-degrading antibodies primary human microglia, non-human primates (NHP), a xenotransplantation model amyloid pathology, we provide evidence that negative regulators both transmembrane proteins. They also negatively regulate microglia proliferation, survival, metabolism, lysosomal function, energetics, phagocytosis, disease-fighting states. Mechanistically, find exerts by interacting protecting it from degradation. turn forms complex blocks co-receptor DAP12, which is required for stability, cell surface localization, signaling other receptors. Taken together, data indicate cooperating, post-transcriptional microglial potential drug targets AD.

Язык: Английский

Процитировано

1