In THP-1 cells, co-stimulation with Aβ and flagellin for 24 h induced up-regulation of TYRO3 and GAS6, which could be prevented by neutralization of TLR5.
We hypothesized that bradykinin receptor inhibition alleviates the vascular dysfunction in a transgenic arcAβ mouse model of cerebral amyloidosis and that fMRI techniques can be used to monitor the treatment response.
The impedimental effect of P33 on the production of beta amyloid (Aβ) (soluble fraction and aggregated plaques) and on the typical features of the AD pathology (decreased dendritic spine density, synaptic markers, elevated inflammatory reactions) was also demonstrated.
Here, we show that amyloid-beta-induced hyperexcitability of hippocampal inhibitory parvalbumin (PV) interneurons importantly contributes to neuronal network dysfunction and memory impairment in APP/PS1 mice, a mouse model of increased amyloidosis.
This study aims to uncover whether ERβ participates in autophagy and promotes extracellular Aβ<sub>1-42</sub> degradation through the autophagy-lysosome system.
This approach is tested using large-scale experimental and structural perturbation analyses in over thirty mutations in three different proteins (cancer-associated NQO1, transthyretin related with amyloidosis and AGT linked to primary hyperoxaluria type I) and comprising five very common pathogenic mechanisms (loss-of-function and gain-of-toxic function aggregation, enzyme inactivation, protein mistargeting and accelerated degradation).
Abbreviations β<sub>2</sub>m β<sub>2</sub>-microglobulin 3D three dimensional AD Alzheimer's disease ADT AutoDock Tools DRA Dialysis-related amyloidosis DSSP dictionary of secondary structure of proteins FEL free energy landscape GROMACS GROningen MAchine for Chemical Simulations LGA Lamarckian Genetic Algorithm LINCS LINear Constraint Solver MC main chain MD molecular dynamics MHC-I major histocompatibility complex class I MM-PBSA molecular mechanics Poisson-Boltzmann surface area PME nanometer (nm); particle mesh ewald PCA principal component analysis PDB protein data bank <i>R</i><sub>g</sub> radius-of-gyration RSV rifamycin SV RMSD root-mean-square deviation RMSF root-mean-square fluctuation SC side chain SPC simple point charge SASA Solvent accessible surface area VMD visual molecular dynamics Communicated by Ramaswamy H. Sarma.
Immunohistochemical and Congo red staining showed that lactadherin and apolipoprotein E were deposited, and that amyloidosis was enhanced in older-aged aortic media.
Abbreviations β<sub>2</sub>m β<sub>2</sub>-microglobulin 3D three dimensional AD Alzheimer's disease ADT AutoDock Tools DRA Dialysis-related amyloidosis DSSP dictionary of secondary structure of proteins FEL free energy landscape GROMACS GROningen MAchine for Chemical Simulations LGA Lamarckian Genetic Algorithm LINCS LINear Constraint Solver MC main chain MD molecular dynamics MHC-I major histocompatibility complex class I MM-PBSA molecular mechanics Poisson-Boltzmann surface area PME nanometer (nm); particle mesh ewald PCA principal component analysis PDB protein data bank <i>R</i><sub>g</sub> radius-of-gyration RSV rifamycin SV RMSD root-mean-square deviation RMSF root-mean-square fluctuation SC side chain SPC simple point charge SASA Solvent accessible surface area VMD visual molecular dynamics Communicated by Ramaswamy H. Sarma.
The impedimental effect of P33 on the production of beta amyloid (Aβ) (soluble fraction and aggregated plaques) and on the typical features of the AD pathology (decreased dendritic spine density, synaptic markers, elevated inflammatory reactions) was also demonstrated.
Adeno-associated virus carrying the CaMK promoter driving the optogenetic channelrhodopsin-2 (CHR2) gene (or without the CHR2 gene, as control) was injected into the bilateral dentate gyri, followed by repeated intrahippocampal injections of soluble low-molecular-weight amyloid-β1-42 peptide (Aβ<sub>1-42</sub>).
Here, we show that absence of TYROBP/DAP12 in a mouse model of AD-type cerebral Aβ amyloidosis (APP<sup>KM670/671NL</sup>/PSEN1<sup>Δexon9</sup>) recapitulates the expected network characteristics by normalizing the transcriptome of APP/PSEN1 mice and repressing the induction of genes involved in the switch from homeostatic microglia to disease-associated microglia (DAM), including Trem2, complement (C1qa, C1qb, C1qc, and Itgax), Clec7a and Cst7.
The mRNA and protein levels of amyloid precursor protein, amyloid-β40 and amyloid-β42 were evaluated by quantitative real-time polymerase chain reaction, western blot assays and enzyme-linked immunosorbent assays. swAPP695-HEK293 cells were transfected with miR-15b-5p mimic, or treated with 1 μM curcumin 24 hours before miR-15b-5p inhibitor transfection.
Abbreviations β<sub>2</sub>m β<sub>2</sub>-microglobulin 3D three dimensional AD Alzheimer's disease ADT AutoDock Tools DRA Dialysis-related amyloidosis DSSP dictionary of secondary structure of proteins FEL free energy landscape GROMACS GROningen MAchine for Chemical Simulations LGA Lamarckian Genetic Algorithm LINCS LINear Constraint Solver MC main chain MD molecular dynamics MHC-I major histocompatibility complex class I MM-PBSA molecular mechanics Poisson-Boltzmann surface area PME nanometer (nm); particle mesh ewald PCA principal component analysis PDB protein data bank <i>R</i><sub>g</sub> radius-of-gyration RSV rifamycin SV RMSD root-mean-square deviation RMSF root-mean-square fluctuation SC side chain SPC simple point charge SASA Solvent accessible surface area VMD visual molecular dynamics Communicated by Ramaswamy H. Sarma.
APOE4 (OR = 3.07 [1.33-7.07], p<sub>unc</sub> < 0.01) was associated with CSF-amyloid in SCD, while it was only predictive for PET-amyloid in MCI (OR = 9.44 [2.93, 30.39], p<sub>FDR</sub> < 0.01).
The impedimental effect of P33 on the production of beta amyloid (Aβ) (soluble fraction and aggregated plaques) and on the typical features of the AD pathology (decreased dendritic spine density, synaptic markers, elevated inflammatory reactions) was also demonstrated.
Collectively, these data indicate that overexpression of ERβ exerts a neuroprotective effect through interacting with ATG7 protein and further enhances autophagy-lysosomal activity for Aβ<sub>1-42</sub> clearance at the cellular level.