TSPO deficiency accelerates amyloid pathology and neuroinflammation by impairing microglial phagocytosis

Zhang, Han; Wang, Huaishan; Gao, Fengmei; Yang, Jia; Xu, Yi; Fu, Yi; Cai, Mengli; Zhang, Xue; Yang, Qi; Tong, Kexin; Hu, Yu; Chen, Hui; Ma, Chao; He, Wei; Zhang, Jianmin

doi:10.1016/j.neurobiolaging.2021.06.020

Cited by 13 publications

(7 citation statements)

References 45 publications

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“…Murine colon sections were prepared for multiplex immunohistochemistry staining as described previously [ 28 ]. Briefly, the sections were deparaffinized through xylenes and rehydrated through decreasing graded alcohol.…”

Section: Methodsmentioning

confidence: 99%

TSPO Deficiency Exacerbates GSDMD-Mediated Macrophage Pyroptosis in Inflammatory Bowel Disease

Zhang

Han

et al. 2022

Cells

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Background: the 18-kDa translocator protein (TSPO) is a mitochondrial outer membrane protein, and its expression tends to increase in response to inflammatory stimulation, rapidly. However, the role of TSPO in inflammation and pyroptosis is not yet clear. Here, we identified TSPO as a novel key regulator of pyroptosis. (2) Methods: TSPO knockout and DSS induced mouse inflammatory bowel disease (IBD) models were employed to assess the roles of TSPO in the pathogenesis of IBD. Primary peritoneal macrophages from TSPO knockout mice were applied to evaluate the mechanism of TSPO in cell pyroptosis. Conclusions: in response to inflammatory injury, TSPO expression is rapidly upregulated and provides a protective function against GSDMD-mediated pyroptosis, which helps us better understand the biological role of TSPO and a novel regulatory mechanism of the pyroptosis process.

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Section: Methodsmentioning

confidence: 99%

TSPO Deficiency Exacerbates GSDMD-Mediated Macrophage Pyroptosis in Inflammatory Bowel Disease

Zhang

Han

et al. 2022

Cells

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“…TSPO is shown to be increased in postmortem brain samples from patients with AD (Venneti et al, 2009 ; Gui et al, 2020 ), which is consistent with our study. TSPO deficiency does not affect Aβ production, but it does accelerate Aβ deposition, leading to more senile plaques (Zhang H. et al, 2021 ). Studies have shown the presence of the rs6971 single nucleotide polymorphism (SNP) in TSPO , which produces different radioligand binding affinities (Owen et al, 2011 ; Tournier et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Hub Genes, Diagnostic Model, and Predicted Drugs Related to Iron Metabolism in Alzheimer's Disease

Lai

Liu

et al. 2022

Front. Aging Neurosci.

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Alzheimer's disease (AD), the most common neurodegenerative disease, remains unclear in terms of its underlying causative genes and effective therapeutic approaches. Meanwhile, abnormalities in iron metabolism have been demonstrated in patients and mouse models with AD. Therefore, this study sought to find hub genes based on iron metabolism that can influence the diagnosis and treatment of AD. First, gene expression profiles were downloaded from the GEO database, including non-demented (ND) controls and AD samples. Fourteen iron metabolism-related gene sets were downloaded from the MSigDB database, yielding 520 iron metabolism-related genes. The final nine hub genes associated with iron metabolism and AD were obtained by differential analysis and WGCNA in brain tissue samples from GSE132903. GO analysis revealed that these genes were mainly involved in two major biological processes, autophagy and iron metabolism. Through stepwise regression and logistic regression analyses, we selected four of these genes to construct a diagnostic model of AD. The model was validated in blood samples from GSE63061 and GSE85426, and the AUC values showed that the model had a relatively good diagnostic performance. In addition, the immune cell infiltration of the samples and the correlation of different immune factors with these hub genes were further explored. The results suggested that these genes may also play an important role in immunity to AD. Finally, eight drugs targeting these nine hub genes were retrieved from the DrugBank database, some of which were shown to be useful for the treatment of AD or other concomitant conditions, such as insomnia and agitation. In conclusion, this model is expected to guide the diagnosis of patients with AD by detecting the expression of several genes in the blood. These hub genes may also assist in understanding the development and drug treatment of AD.

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“…Translocator protein is involved in the phagocytotic ability of microglia. Microglia taken from TSPO knockout mice had impaired phagocytosis, which led to the accumulation of β-amyloid that was not properly cleared and removed ( Zhang et al, 2021 ). This may be a result of the high energy demand of cytoskeletal reorganization during phagocytosis, where a decrease in energy production was accompanied by impaired phagocytosis ( Yao et al, 2020 ; Fairley et al, 2023 ).…”

Section: Tspo In Glial Regulation Of Neuronal Healthmentioning

confidence: 99%

Translocator protein in the rise and fall of central nervous system neurons

Cheung

Lin

Papadopoulos

2023

Front. Cell. Neurosci.

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Translocator protein (TSPO), a 18 kDa protein found in the outer mitochondrial membrane, has historically been associated with the transport of cholesterol in highly steroidogenic tissues though it is found in all cells throughout the mammalian body. TSPO has also been associated with molecular transport, oxidative stress, apoptosis, and energy metabolism. TSPO levels are typically low in the central nervous system (CNS), but a significant upregulation is observed in activated microglia during neuroinflammation. However, there are also a few specific regions that have been reported to have higher TSPO levels than the rest of the brain under normal conditions. These include the dentate gyrus of the hippocampus, the olfactory bulb, the subventricular zone, the choroid plexus, and the cerebellum. These areas are also all associated with adult neurogenesis, yet there is no explanation of TSPO’s function in these cells. Current studies have investigated the role of TSPO in microglia during neuron degeneration, but TSPO’s role in the rest of the neuron lifecycle remains to be elucidated. This review aims to discuss the known functions of TSPO and its potential role in the lifecycle of neurons within the CNS.

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TSPO deficiency accelerates amyloid pathology and neuroinflammation by impairing microglial phagocytosis

Cited by 13 publications

References 45 publications

TSPO Deficiency Exacerbates GSDMD-Mediated Macrophage Pyroptosis in Inflammatory Bowel Disease

TSPO Deficiency Exacerbates GSDMD-Mediated Macrophage Pyroptosis in Inflammatory Bowel Disease

Hub Genes, Diagnostic Model, and Predicted Drugs Related to Iron Metabolism in Alzheimer's Disease

Translocator protein in the rise and fall of central nervous system neurons

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