Genetic Ablation of Hematopoietic Cell Kinase Accelerates Alzheimer’s Disease–Like Neuropathology in Tg2576 Mice

Lim, Siok Lam; Tran, Diana; Kieu, Zanett; Chen, Christine; Villanueva, Emmanuel; Ghiaar, Sagar; Gallup, Victoria; Zumkehr, Joannee; Cribbs, David H.; Rodriguez‐Ortiz, Carlos J.; Kitazawa, Masashi

doi:10.1007/s12035-020-01894-6

Cited by 8 publications

(7 citation statements)

References 63 publications

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“…It has been reported that hematopoietic microglia can ameliorate the progression of AD by eliminating amyloid deposition through cell-specific phagocytic mechanisms ( Lampron et al, 2011 ). Furthermore, hematopoietic cells and their associated factors have potential therapeutic value in AD, and the downregulation of the relative number of hematopoietic cells may be one of the critical theories ( Sanchez-Ramos et al, 2008 ; Lim et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

Application of Artificial Intelligence Modeling Technology Based on Fluid Biopsy to Diagnose Alzheimer’s Disease

Liu

Jian-hu

et al. 2021

Front. Aging Neurosci.

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Background: There are no obvious clinical signs and symptoms in the early stages of Alzheimer’s disease (AD), and most patients usually have mild cognitive impairment (MCI) before diagnosis. Therefore, early diagnosis of AD is very critical. This paper mainly discusses the blood biomarkers of AD patients and uses machine learning methods to study the changes of blood transcriptome during the development of AD and to search for potential blood biomarkers for AD.Methods: Individualized blood mRNA expression data of 711 patients were downloaded from the GEO database, including the control group (CON) (238 patients), MCI (189 patients), and AD (284 patients). Firstly, we analyzed the subcellular localization, protein types and enrichment pathways of the differentially expressed mRNAs in each group, and established an artificial intelligence individualized diagnostic model. Furthermore, the XCell tool was used to analyze the blood mRNA expression data and obtain blood cell composition and quantitative data. Ratio characteristics were established for mRNA and XCell data. Feature engineering operations such as collinearity and importance analysis were performed on all features to obtain the best feature solicitation. Finally, four machine learning algorithms, including linear support vector machine (SVM), Adaboost, random forest and artificial neural network, were used to model the optimal feature combinations and evaluate their classification performance in the test set.Results: Through feature engineering screening, the best feature collection was obtained. Moreover, the artificial intelligence individualized diagnosis model established based on this method achieved a classification accuracy of 91.59% in the test set. The area under curve (AUC) of CON, MCI, and AD were 0.9746, 0.9536, and 0.9807, respectively.Conclusion: The results of cell homeostasis analysis suggested that the homeostasis of Natural killer T cell (NKT) might be related to AD, and the homeostasis of Granulocyte macrophage progenitor (GMP) might be one of the reasons for AD.

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Section: Resultsmentioning

confidence: 99%

Application of Artificial Intelligence Modeling Technology Based on Fluid Biopsy to Diagnose Alzheimer’s Disease

Liu

Jian-hu

et al. 2021

Front. Aging Neurosci.

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“…Similarly, the results of phagocytosis and platelet activation of these proteins were also reported. Studies have shown that Hck deficiency weakens the phagocytic function of microglia a β ( Lim et al., 2020 ). Hck is one of the key regulators of phagocytosis among the Src family tyrosine kinases (SFKs) in myeloid cells and combined absence of the Src family kinases Hck drastically impairs phagocytosis ( Lim et al., 2018 ; Lőrincz et al., 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Alleviation of Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome in Rats by Yiqi Huayu Jiedu Decoction: A Tandem Mass Tag-Based Proteomics Study

Luo

et al. 2020

Front. Pharmacol.

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Background To study the effect of Yiqi Huayu Jiedu Decoction (YQHYJD) on protein expression in the lung tissue of acute respiratory distress syndrome (ARDS) rats and to explore the underlying molecular therapeutic mechanism of YQHYJD. Methods Sprague Dawley rats were administered with YQHYJD by oral gavage for 1 week. The rats were injected with lipopolysaccharide (LPS) to induce ARDS. The lung injury was assessed pathologically. Differentially expressed proteins (DEPs) were screened by quantitative proteomics and analyzed using bioinformatic tools, such as Metascape and Kyoto Encyclopedia of Genes and Genomes (KEGG) mapper. DEPs were verified by parallel reaction monitoring (PRM). Results YQHYJD alleviated the LPS-induced pathological damage of lung tissue in rats. There were 134 DEPs among the YQHYJD treatment and model groups. The Genomes pathway analyses revealed that the DEPs were closely related to immune system pathway. The mass spectrometry analysis revealed that YQHYJD exhibits a protective effect on lung tissue by significantly upregulating hematopoietic cell kinase (Hck), phospholipid phosphatase 3 (Plpp3), myristoylated-alanine rich C-kinase substrate (Marcks), and Actin-related protein 2/3 complex subunit 2 (Arpc2), which are related to Fc gamma receptor-mediated phagocytosis pathway. Conclusion YQHYJD can alleviate the lung injury of ARDS rats by regulating the Fc gamma receptor-mediated phagocytosis pathway, which is related to immune system.

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“…Considering that activation of tyrosine kinases is a critical signaling step in various processes essential for immune cell function, including proliferation and inflammatory responses, it is reasonable to conjecture that alteration of SFK activity by toxic amyloid species might be involved in the AD neurodegenerative process. This premise is corroborated using complementary genetic [121,129–131] and pharmacological [43,88,124,132] approaches, suggesting that modulating the activation of SFKs affects pathology in animal models of AD.…”

Section: Sfks Microglia and Neurodegenerationmentioning

confidence: 89%

Src family kinases (SFKs): critical regulators of microglial homeostatic functions and neurodegeneration in Parkinson's and Alzheimer's diseases

et al. 2021

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c‐Src was the first protein kinase to be described as capable of phosphorylating tyrosine residues. Subsequent identification of other tyrosine‐phosphorylating protein kinases with a similar structure to c‐Src gave rise to the concept of Src family kinases (SFKs). Microglia are the resident innate immune cell population of the CNS. Under physiological conditions, microglia actively participate in brain tissue homeostasis, continuously patrolling the neuronal parenchyma and exerting neuroprotective actions. Activation of pathogen‐associated molecular pattern (PAMP) and damage‐associated molecular pattern (DAMP) receptors induces microglial proliferation, migration toward pathological foci, phagocytosis, and changes in gene expression, concurrent with the secretion of cytokines, chemokines, and growth factors. A significant body of literature shows that SFK stimulation positively associates with microglial activation and neuropathological conditions, including Alzheimer's and Parkinson's diseases. Here, we review essential microglial homeostatic functions regulated by SFKs, including phagocytosis, environmental sensing, and secretion of inflammatory mediators. In addition, we discuss the potential of SFK modulation for microglial homeostasis in Parkinson's and Alzheimer's diseases.

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Genetic Ablation of Hematopoietic Cell Kinase Accelerates Alzheimer’s Disease–Like Neuropathology in Tg2576 Mice

Cited by 8 publications

References 63 publications

Application of Artificial Intelligence Modeling Technology Based on Fluid Biopsy to Diagnose Alzheimer’s Disease

Application of Artificial Intelligence Modeling Technology Based on Fluid Biopsy to Diagnose Alzheimer’s Disease

Alleviation of Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome in Rats by Yiqi Huayu Jiedu Decoction: A Tandem Mass Tag-Based Proteomics Study

Src family kinases (SFKs): critical regulators of microglial homeostatic functions and neurodegeneration in Parkinson's and Alzheimer's diseases

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