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Cited by 101Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsCell Adhesion Molecules Research

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Filamentous recombinant human Tau activates primary astrocytes via an integrin receptor complex

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Wang, Peng, Ye, Yihong·2021·Nature Communications
DOI 10.1038/s41467-020-20322-wPMC PMC7782792

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Abstract

Microtubule-associated protein Tau can form protein aggregates transmissible within the brain, correlating with the progression of tauopathies in humans. The transmission of aggregates requires neuron-released Tau to interact with surface receptors on target cells. However, the underlying molecular mechanisms in astrocytes and downstream effects are unclear. Here, using a spatially resolved proteomic mapping strategy, we show that integrin αV/β1 receptor binds recombinant human Tau, mediating the entry of Tau fibrils in astrocytes. The binding of distinct Tau species to the astrocytic αV/β1 receptor differentially activate integrin signaling. Furthermore, Tau-mediated activation of integrin signaling results in NFκB activation, causing upregulation of pro-inflammatory cytokines and chemokines, induction of a sub-group of neurotoxic astrocytic markers, and release of neurotoxic factors. Our findings suggest that filamentous recombinant human Tau-mediated activation of integrin signaling induces astrocyte conversion towards a neurotoxic state, providing a mechanistic insight into tauopathies.

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Fig. 1 Identification of integrin αV/β1 as a Tau interactor in primary astrocytes. a Schematic overview of the proximity-based proteomic mapping strategy. Tau-APEX2 (200 nM) is bound to the cell surface. Biotinylation was initiated by incubating cells with biotin-phenol (BP) in the presence of H2O2 for 4 min. Biotinylated proteins were then purified by affinity chromatography using streptavidin resin. b Coomassie blue staining of purified Tau proteins. c Coomassie blue staining (left) and immunoblotting (IB) (right) of biotinylated proteins from primary astrocytes incubated with APEX2 or Tau-APEX2. The arrow indicates a 120 kDa protein detected in Tau-APEX2-treated cells. d, e Validation of Tau-APEX2-mediated biotinylation of ITGαV/β1. d Tau-APEX2 was incubated with HEK293T cells transfected with either an empty vector (EV) or ITGαV-Flag. Whole cell extracts (WCE) were either directly analyzed by immunoblotting or first subjected to biotin pulldown (Bio-PD) before immunoblotting. e Whole cell extracts (WCE) from primary astrocytes treated with either APEX2 or Tau-APEX2 were analyzed directly by immunoblotting or first subjected to biotin pulldown before immunoblotting. f Co-immunoprecipitation of Tau-APEX2 with ITGαVβ1. Astrocytes were treated with Tau-APEX2 (200 nM) or PBS as a control for 30 min on ice. Cells were lysed in an NP40-containing lysis buffer. Cell lysates were subjected to immunoprecipitation with either a control IgG or a Tau specific antibody (Tau-46). Both cell lysates and precipitated proteins were analyzed by immunoblotting. Where indicated, a fraction of the remaining medium was also analyzed by immunoblotting to show input.
Fig. 1 Identification of integrin αV/β1 as a Tau interactor in primary astrocytes. a Schematic overview of the proximity-based proteomic mapping strategy. Tau-APEX2 (200 nM) is bound to the cell surface. Biotinylation was initiated by incubating cells with biotin-phenol (BP) in the presence of H2O2 for 4 min. Biotinylated proteins were then purified by affinity chromatography using streptavidin resin. b Coomassie blue staining of purified Tau proteins. c Coomassie blue staining (left) and immunoblotting (IB) (right) of biotinylated proteins from primary astrocytes incubated with APEX2 or Tau-APEX2. The arrow indicates a 120 kDa protein detected in Tau-APEX2-treated cells. d, e Validation of Tau-APEX2-mediated biotinylation of ITGαV/β1. d Tau-APEX2 was incubated with HEK293T cells transfected with either an empty vector (EV) or ITGαV-Flag. Whole cell extracts (WCE) were either directly analyzed by immunoblotting or first subjected to biotin pulldown (Bio-PD) before immunoblotting. e Whole cell extracts (WCE) from primary astrocytes treated with either APEX2 or Tau-APEX2 were analyzed directly by immunoblotting or first subjected to biotin pulldown before immunoblotting. f Co-immunoprecipitation of Tau-APEX2 with ITGαVβ1. Astrocytes were treated with Tau-APEX2 (200 nM) or PBS as a control for 30 min on ice. Cells were lysed in an NP40-containing lysis buffer. Cell lysates were subjected to immunoprecipitation with either a control IgG or a Tau specific antibody (Tau-46). Both cell lysates and precipitated proteins were analyzed by immunoblotting. Where indicated, a fraction of the remaining medium was also analyzed by immunoblotting to show input.CC BY · PubMed Central
Fig. 2 Integrin αV/β1 and Talin1 are required for Tau PFF uptake in astrocytes. a Co-immunoprecipitation of Tau PFF and ITGαV/β1. Astrocytes were treated with Tau PFFs or PBS as a control. Cell lysates were subjected to immunoprecipitation with either a control IgG or a Tau specific antibody (Tau-46). Both lysates and precipitated proteins were analyzed by immunoblotting. Where indicated, a fraction of the medium collected after the binding was also analyzed by immunoblotting. b, c Quantification (mean ± SEM) of mRNA expression by qRT-PCR performed 72 h postlentiviral infection confirmed the knockdown efficiency of ITGαV (b), β1 (c). A.U. arbitrary unit. n = 3 biologically independent experiments. The numbers above indicate p values determined by two-tailed unpaired t-test. d–g Astrocytic uptake of Tau PFF is dependent on ITGαV/β1 and Talin1. f Representative images of lentivirus-treated astrocytes incubated with Alexa594 (Red)-labeled Tau-PFF (200 nM) for 2 h. Cells were stained with Hoechst to label the nuclei (blue). Scale bar, 5 μm. d, e Quantification of the relative Tau PFF fluorescence intensity/cell. Mean ± SEM, n = 3 biologically independent experiments. The numbers and asterisks above indicate p values (****p < 0.0001) determined by two-tailed unpaired t-test. Dots represent the average fluorescence intensity/cell from images (>20 cells/image) acquired. g As in b, except that Talin1 mRNA expression was determined after Talin1 knockdown. Mean ± SEM, n = 4 biologically independent samples. h, i FAK is not required for Tau PFF uptake. h Representative images of DMSO or PF-562271-treated astrocytes (10 µM) incubated with labeled Tau-PFF (200 nM) after 2 h. Scale bar, 5 μm. i Quantification of Tau PFF uptake in h. Mean ± SEM, n = 3 biologically independent experiments. Dots represent average fluorescence intensity/cell from images acquired.
Fig. 2 Integrin αV/β1 and Talin1 are required for Tau PFF uptake in astrocytes. a Co-immunoprecipitation of Tau PFF and ITGαV/β1. Astrocytes were treated with Tau PFFs or PBS as a control. Cell lysates were subjected to immunoprecipitation with either a control IgG or a Tau specific antibody (Tau-46). Both lysates and precipitated proteins were analyzed by immunoblotting. Where indicated, a fraction of the medium collected after the binding was also analyzed by immunoblotting. b, c Quantification (mean ± SEM) of mRNA expression by qRT-PCR performed 72 h postlentiviral infection confirmed the knockdown efficiency of ITGαV (b), β1 (c). A.U. arbitrary unit. n = 3 biologically independent experiments. The numbers above indicate p values determined by two-tailed unpaired t-test. d–g Astrocytic uptake of Tau PFF is dependent on ITGαV/β1 and Talin1. f Representative images of lentivirus-treated astrocytes incubated with Alexa594 (Red)-labeled Tau-PFF (200 nM) for 2 h. Cells were stained with Hoechst to label the nuclei (blue). Scale bar, 5 μm. d, e Quantification of the relative Tau PFF fluorescence intensity/cell. Mean ± SEM, n = 3 biologically independent experiments. The numbers and asterisks above indicate p values (****p < 0.0001) determined by two-tailed unpaired t-test. Dots represent the average fluorescence intensity/cell from images (>20 cells/image) acquired. g As in b, except that Talin1 mRNA expression was determined after Talin1 knockdown. Mean ± SEM, n = 4 biologically independent samples. h, i FAK is not required for Tau PFF uptake. h Representative images of DMSO or PF-562271-treated astrocytes (10 µM) incubated with labeled Tau-PFF (200 nM) after 2 h. Scale bar, 5 μm. i Quantification of Tau PFF uptake in h. Mean ± SEM, n = 3 biologically independent experiments. Dots represent average fluorescence intensity/cell from images acquired.CC BY · PubMed Central
Fig. 3 Monomeric and filamentous Tau differentially activate integrin signaling. a, b Tau PFF activates integrin signaling in an ITGαV/β1 dependent manner. qRT-PCR analyses of the expression of a collection of integrin target genes in primary astrocytes. Cells were first infected with either control or ITGαV/β1 shRNA for 72 h and then treated with PBS, monomeric Tau, or Tau PFFs (200 nM) for 6 h. Shown are fold changes (FC) normalized to PBS-treated samples. a A comparison between Tau monomer and PFF. b A comparison of Tau PFF treatment in control vs. ITGαV/β1 knockdown cells. Mean ± SEM, n = 3 independent experiments, each with two technical repeats. c A schematic overview of the immuno-panning strategy for purification of astrocytes using anti-ITGβ5 antibodies. Briefly, cortical cell suspensions were passed successively over secondary antibody-coated and anti-CD45-coated plates to remove macrophages and microglia, and then plated in a positive selection panning plate for astrocytes (anti-ITGβ5 coated). The lower panel shows a representative immunofluorescence image of purified astrocytes treated with Tau PFF Alexa594 (200 nM) (Magenta) 1 h and then stained with anti-GFAP antibodies (Green) and Hoechst (Blue). Scale bar, 5 μm. d Talin1 is required for Tau PFF-induced integrin signaling. As in b, except that immunopurified astrocytes were first infected with either control- or Talin1 shRNA-expressing lentivirus and then treated with Tau PFF. Mean ± SEM n = 3 independent experiments, each with two technical repeats. The numbers and asterisks above indicate p value (****p < 0.0001) determined by two-tailed unpaired t-test.
Fig. 3 Monomeric and filamentous Tau differentially activate integrin signaling. a, b Tau PFF activates integrin signaling in an ITGαV/β1 dependent manner. qRT-PCR analyses of the expression of a collection of integrin target genes in primary astrocytes. Cells were first infected with either control or ITGαV/β1 shRNA for 72 h and then treated with PBS, monomeric Tau, or Tau PFFs (200 nM) for 6 h. Shown are fold changes (FC) normalized to PBS-treated samples. a A comparison between Tau monomer and PFF. b A comparison of Tau PFF treatment in control vs. ITGαV/β1 knockdown cells. Mean ± SEM, n = 3 independent experiments, each with two technical repeats. c A schematic overview of the immuno-panning strategy for purification of astrocytes using anti-ITGβ5 antibodies. Briefly, cortical cell suspensions were passed successively over secondary antibody-coated and anti-CD45-coated plates to remove macrophages and microglia, and then plated in a positive selection panning plate for astrocytes (anti-ITGβ5 coated). The lower panel shows a representative immunofluorescence image of purified astrocytes treated with Tau PFF Alexa594 (200 nM) (Magenta) 1 h and then stained with anti-GFAP antibodies (Green) and Hoechst (Blue). Scale bar, 5 μm. d Talin1 is required for Tau PFF-induced integrin signaling. As in b, except that immunopurified astrocytes were first infected with either control- or Talin1 shRNA-expressing lentivirus and then treated with Tau PFF. Mean ± SEM n = 3 independent experiments, each with two technical repeats. The numbers and asterisks above indicate p value (****p < 0.0001) determined by two-tailed unpaired t-test.CC BY · PubMed Central
Fig. 4 Tau PFF induces inflammation in astrocytes via the integrin pathway. a–c Tau PFF induces astrocytic inflammation in an ITGαV/β1 dependent manner. qRT-PCR analyses of the expression of inflammation-associated cytokine and chemokine genes in primary astrocytes. Cells were first infected with either control shRNA (a, b) or control and ITGαV/β1 shRNA (c) for 72 h and then incubated with PBS, monomeric Tau or Tau PFFs (200 nM) for 6 h. Shown are fold changes (FC) normalized to PBS-treated cells. Mean ± SEM, n = 3 independent experiments, each with two technical repeats. d, e Tau PFF induces NOS2 expression in an ITGαV/β1 dependent manner. d As in a, except that NOS2 mRNA was analyzed. Mean ± SEM, n = 3. Dashed lines indicate individual experiment. e As in c, except that NOS2 mRNA was analyzed. The number indicates p value determined by two-tailed unpaired t-test. f–h qRT-PCR analyses of the expression of pro-inflammation-related cytokines (f, g) and chemokines (h) in immunopurified astrocytes. Cells were infected with either a control or Talin1 (TLN1)-specific shRNA prior to the treatment with either PBS or Tau PFFs (200 nM) for 6 h. Fold changes (FC) were normalized to PBS-treated samples. Mean ± SEM, n = 6 (f, g) or n = 5 (h) independent experiments, each with two technical duplicates. i As in f, except that NOS2 mRNA was analyzed. Mean ± SEM, n = 5 independent experiments. j, k qRT-PCR analyses of the expression of the indicated pro-inflammation cytokines (j) or chemokines (k) in immunopurified astrocytes that were treated with DMSO or PF-562271 (1 μM) for 1 h before incubation with PBS or Tau PFF (200 nM) for 6 h. Fold changes (FC) were normalized to PBS-treated samples. Mean ± SEM, n = 4 (j) or 3 (k) independent experiments each with two technical duplicates. The numbers and asterisks above indicate p value (****p < 0.0001) determined by two-tailed unpaired t-test.
Fig. 4 Tau PFF induces inflammation in astrocytes via the integrin pathway. a–c Tau PFF induces astrocytic inflammation in an ITGαV/β1 dependent manner. qRT-PCR analyses of the expression of inflammation-associated cytokine and chemokine genes in primary astrocytes. Cells were first infected with either control shRNA (a, b) or control and ITGαV/β1 shRNA (c) for 72 h and then incubated with PBS, monomeric Tau or Tau PFFs (200 nM) for 6 h. Shown are fold changes (FC) normalized to PBS-treated cells. Mean ± SEM, n = 3 independent experiments, each with two technical repeats. d, e Tau PFF induces NOS2 expression in an ITGαV/β1 dependent manner. d As in a, except that NOS2 mRNA was analyzed. Mean ± SEM, n = 3. Dashed lines indicate individual experiment. e As in c, except that NOS2 mRNA was analyzed. The number indicates p value determined by two-tailed unpaired t-test. f–h qRT-PCR analyses of the expression of pro-inflammation-related cytokines (f, g) and chemokines (h) in immunopurified astrocytes. Cells were infected with either a control or Talin1 (TLN1)-specific shRNA prior to the treatment with either PBS or Tau PFFs (200 nM) for 6 h. Fold changes (FC) were normalized to PBS-treated samples. Mean ± SEM, n = 6 (f, g) or n = 5 (h) independent experiments, each with two technical duplicates. i As in f, except that NOS2 mRNA was analyzed. Mean ± SEM, n = 5 independent experiments. j, k qRT-PCR analyses of the expression of the indicated pro-inflammation cytokines (j) or chemokines (k) in immunopurified astrocytes that were treated with DMSO or PF-562271 (1 μM) for 1 h before incubation with PBS or Tau PFF (200 nM) for 6 h. Fold changes (FC) were normalized to PBS-treated samples. Mean ± SEM, n = 4 (j) or 3 (k) independent experiments each with two technical duplicates. The numbers and asterisks above indicate p value (****p < 0.0001) determined by two-tailed unpaired t-test.CC BY · PubMed Central
Fig. 5 Tau PFF-induced inflammation is dependent on NFκB activation. a qRT-PCR analyses of the expression of NFκB and STAT3 in primary astrocytes exposed to PBS, monomeric Tau or Tau PFFs (200 nM) for 6 h. Shown are fold changes (FC) normalized to PBS-treated cells. Mean ± SEM, n = 3 independent experiments each with two technical repeats. b, c As in a, except that cells were first infected with control or ITGαV/β1 shRNA (b), or Talin1 shRNA (c) for 72 h and then incubated with PBS or Tau PFFs (200 nM) for 6 h. Mean ± SEM, n = 3 independent experiments. d As in b, except that control-treated or PF-562271-treated astrocytes were used. Mean ± SEM, n = 3 independent experiments. e–g Tau PFF increases NFκB nuclear translocation. e Representative confocal images of astrocytes treated with either PBS, Tau monomer, PFFs (200 nM) for 4 h or LPS as a positive control (5 μM) for 30 min. Cell were fixed and stained with a NFκB antibody and Hoechst (blue). The graphs in f show the fluorescence intensity profile along the lines indicated in e. The blue bars indicate nuclear regions. g Quantification of the nuclear/cytoplasmic NFκB ratio in randomly selected cells. Mean ± SEM, n = 3 biologically independent experiments. h, i Tau PFF-induced inflammation is suppressed by a NFκB inhibitor. As in d, except that cells were pre-treated with PDTC (90 μM) for 1 h before Tau PFF and PBS treatment and that the indicated genes were analyzed. Mean ± SEM, n = 3 independent experiments. The numbers and asterisks above indicate p value (****p < 0.0001) determined by two-tailed unpaired t-test.
Fig. 5 Tau PFF-induced inflammation is dependent on NFκB activation. a qRT-PCR analyses of the expression of NFκB and STAT3 in primary astrocytes exposed to PBS, monomeric Tau or Tau PFFs (200 nM) for 6 h. Shown are fold changes (FC) normalized to PBS-treated cells. Mean ± SEM, n = 3 independent experiments each with two technical repeats. b, c As in a, except that cells were first infected with control or ITGαV/β1 shRNA (b), or Talin1 shRNA (c) for 72 h and then incubated with PBS or Tau PFFs (200 nM) for 6 h. Mean ± SEM, n = 3 independent experiments. d As in b, except that control-treated or PF-562271-treated astrocytes were used. Mean ± SEM, n = 3 independent experiments. e–g Tau PFF increases NFκB nuclear translocation. e Representative confocal images of astrocytes treated with either PBS, Tau monomer, PFFs (200 nM) for 4 h or LPS as a positive control (5 μM) for 30 min. Cell were fixed and stained with a NFκB antibody and Hoechst (blue). The graphs in f show the fluorescence intensity profile along the lines indicated in e. The blue bars indicate nuclear regions. g Quantification of the nuclear/cytoplasmic NFκB ratio in randomly selected cells. Mean ± SEM, n = 3 biologically independent experiments. h, i Tau PFF-induced inflammation is suppressed by a NFκB inhibitor. As in d, except that cells were pre-treated with PDTC (90 μM) for 1 h before Tau PFF and PBS treatment and that the indicated genes were analyzed. Mean ± SEM, n = 3 independent experiments. The numbers and asterisks above indicate p value (****p < 0.0001) determined by two-tailed unpaired t-test.CC BY · PubMed Central
Fig. 6 Tau PFF converts astrocytes to a neurotoxic state in an integrin-dependent manner. a A heat map shows the expression of pan-reactive, A1 and A2 signature genes in Tau monomer- and PFF-treated primary astrocytes (200 nM, 6 h), which is normalized to PBS-treated cells. Shown is the average of three independent experiments. Asterisks indicate p value (*p < 0.05; **p < 0.01; ***p < 0.001) from two-tailed unpaired t-test. b The expression of the indicated A1 genes were analyzed by qRT-PCR from PBS- or Tau PFF-treated (200 nM, 6 h) astrocytes, which had been infected with lentiviruses (72 h) expressing control or ITGαV/β1 shRNAs. Fold changes (FC) were normalized to PBS-treated samples. Mean ± SEM, n = 3 independent experiments each with two technical duplicates. c As in b, except that immunopurified astrocytes infected with control-expressing or Talin1 (TLN1) shRNA-expressing lentiviruses were used. Mean ± SEM, n = 4 biologically independent samples. d As in c, except that cells were treated with DMSO or PF-562271 (1 μM, 1 h) instead of lentivirus prior to PBS or Tau PFF treatment. Mean ± SEM, n = 3 biologically independent samples, each with two technical duplicates. e Tau PFF-induced A1 genes is suppressed by a NFκB inhibitor. As in d, except that cells were treated with PDTC (90 μM) for 1 h before Tau PFF and PBS treatment. Mean ± SEM, n = 3 biologically independent samples. The numbers above indicate p value determined by two-tailed unpaired t-test.
Fig. 6 Tau PFF converts astrocytes to a neurotoxic state in an integrin-dependent manner. a A heat map shows the expression of pan-reactive, A1 and A2 signature genes in Tau monomer- and PFF-treated primary astrocytes (200 nM, 6 h), which is normalized to PBS-treated cells. Shown is the average of three independent experiments. Asterisks indicate p value (*p < 0.05; **p < 0.01; ***p < 0.001) from two-tailed unpaired t-test. b The expression of the indicated A1 genes were analyzed by qRT-PCR from PBS- or Tau PFF-treated (200 nM, 6 h) astrocytes, which had been infected with lentiviruses (72 h) expressing control or ITGαV/β1 shRNAs. Fold changes (FC) were normalized to PBS-treated samples. Mean ± SEM, n = 3 independent experiments each with two technical duplicates. c As in b, except that immunopurified astrocytes infected with control-expressing or Talin1 (TLN1) shRNA-expressing lentiviruses were used. Mean ± SEM, n = 4 biologically independent samples. d As in c, except that cells were treated with DMSO or PF-562271 (1 μM, 1 h) instead of lentivirus prior to PBS or Tau PFF treatment. Mean ± SEM, n = 3 biologically independent samples, each with two technical duplicates. e Tau PFF-induced A1 genes is suppressed by a NFκB inhibitor. As in d, except that cells were treated with PDTC (90 μM) for 1 h before Tau PFF and PBS treatment. Mean ± SEM, n = 3 biologically independent samples. The numbers above indicate p value determined by two-tailed unpaired t-test.CC BY · PubMed Central
Fig. 7 Tau PFF-treated astrocytes release a neurotoxic factor(s) via ITGαV/β1 activation. a Scheme of the cell toxicity assay. b, c Primary cortical neurons at DIV 10 were treated with the indicated condition medium (CM) for 72 h and stained with a green-fluorescent dye calcein-AM to label viable cells and a red-fluorescent dye ethidium homodimer-1 to label dead cells. b Representative images. Scale bar, 10 μm. c Quantification of dead cells labeled by ethidium homodimer-1 in randomly selected fields. Mean ± SEM, n = 3 biologically independent samples. The numbers and asterisks above indicate p value (****p < 0.0001) determined by two-tailed unpaired t-test. d A working model showing the interplays between Tau-PFF, astrocytes and neurons.
Fig. 7 Tau PFF-treated astrocytes release a neurotoxic factor(s) via ITGαV/β1 activation. a Scheme of the cell toxicity assay. b, c Primary cortical neurons at DIV 10 were treated with the indicated condition medium (CM) for 72 h and stained with a green-fluorescent dye calcein-AM to label viable cells and a red-fluorescent dye ethidium homodimer-1 to label dead cells. b Representative images. Scale bar, 10 μm. c Quantification of dead cells labeled by ethidium homodimer-1 in randomly selected fields. Mean ± SEM, n = 3 biologically independent samples. The numbers and asterisks above indicate p value (****p < 0.0001) determined by two-tailed unpaired t-test. d A working model showing the interplays between Tau-PFF, astrocytes and neurons.CC BY · PubMed Central

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Metadata

Authors
Wang, P., & Ye, Y.
Affiliations
National Institutes of Health (US)
Corresponding author
Ye, Yihong
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2021-01-04
Volume
12
Issue
1
Pages
95-95
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-020-20322-w
PMC
PMC7782792
OpenAlex
W3118652952
Cited by
93
References
75
Citations by year
2026: 11 · 2025: 19 · 2024: 17 · 2023: 15 · 2022: 20 · 2021: 10
FWCI
10.98
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
Keywords
tau protein, tauopathy, astrocytes, integrin αvβ1, integrin signaling, tau fibrils, NF-κB activation, inflammatory cytokines, chemokines, neuroinflammation
MeSH terms
Animals, Astrocytes, Cells, Cultured, Humans, Inflammation, Mice, Inbred C57BL, Neurons, Protein Binding, Recombinant Proteins, Signal Transduction, NF-kappa B, Talin, tau Proteins, Receptors, Vitronectin, Heparan Sulfate Proteoglycans, STAT3 Transcription Factor, Mice, Focal Adhesion Protein-Tyrosine Kinases, HEK293 Cells

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