tfeb activator ta1  (MedChemExpress)

Journal: Alzheimer's Research & Therapy

Article Title: Intermittent hypoxia training enhances Aβ endocytosis by plaque associated microglia via VPS35-dependent TREM2 recycling in murine Alzheimer’s disease

doi: 10.1186/s13195-024-01489-6

Figure Lengend Snippet: TFEB transcriptionally regulates Vps35 in BV2 cells. ( A ) A consensus TFEB-binding motif within the ChIP-seq peaks. ( B ) ChIP-PCR was performed to identify potential TFEB-binding elements in the Vps35 gene regulatory regions. IgG was used as a negative control. ( C ) ChIP-qPCR was conducted to detect the fold enrichment of the three identified CLEAR elements. ( D ) Sequences of ChIP-based CLEAR elements and mutants. ( E ) Dual luciferase activities of the constructs containing the promoter region of Vps35 with either intact (WT) or mutated (Mut) CLEAR elements were compared between shControl (NC) and sh TFEB HEK293T cells. ( F and G ) Tfeb and Vps35 expressions in TA1-treated sh Tfeb BV2 cells were estimated with qRT-PCR. n = 3, * p < 0.05 and *** p < 0.001 by Student’s t -test ( C ) or two-way ANOVA ( E to G ). n.s. indicates no significant difference

Article Snippet: TA1 (MedChemExpress, HY-135,825, CAS: 39777-61-2, 99.69% purity) was dissolved in DMSO to a concentration of 25 mg/ml and further diluted 10-fold with corn oil to 2.5 mg/ml for animal treatment.

Techniques: Binding Assay, ChIP-sequencing, Negative Control, ChIP-qPCR, Luciferase, Construct, Quantitative RT-PCR

Journal: Alzheimer's Research & Therapy

Article Title: Intermittent hypoxia training enhances Aβ endocytosis by plaque associated microglia via VPS35-dependent TREM2 recycling in murine Alzheimer’s disease

doi: 10.1186/s13195-024-01489-6

Figure Lengend Snippet: IHT-induced attenuation of Aβ pathology and amelioration of Aβ endocytosis by DAM depends on TFEB. 9-month-old APP/PS1 mice were treated with TA1. ( A ) Brain sections of TA1-treated APP/PS1 mice were stained with anti-TFEB/anti-VPS35/anti-TREM2 and anti-Iba1 antibodies, and microscopy images of DAM in CA1 region were captured. Scale bar = 20 μm. ( B to D ) TFEB ( B ), VPS35 ( C ), and TREM2 ( D ) intensities in the DAM in panel A (six mice in each group, with 10 cells per mouse). ( E ) Sh Tfeb BV2 cells were used to construct Aβ-exposed microglia and then treated with IHT. TFEB and VPS35 expression levels were detected via Western blotting. ( F ) Grayscale values of the protein bands in panel E ( n = 3). ( G ) After treatment with IHT, sh Tfeb Aβ-exposed microglia were incubated with Aβ-555 for 30 min, followed by fixation and counterstaining with DAPI. Scale bar = 10 μm. ( H ) Aβ-555 intensity in the GFP + cells in panel G ( n > 50). * p < 0.05, ** p < 0.01, and *** p < 0.001 by Student’s t -test ( B to D ) or two-way ANOVA ( F , H ). n.s. indicates no significant difference. Nor, normoxia; IHT, intermittent hypoxia training

Article Snippet: TA1 (MedChemExpress, HY-135,825, CAS: 39777-61-2, 99.69% purity) was dissolved in DMSO to a concentration of 25 mg/ml and further diluted 10-fold with corn oil to 2.5 mg/ml for animal treatment.

Techniques: Staining, Microscopy, Construct, Expressing, Western Blot, Incubation