Previously, we showed that replacing endogenous p35 with the noncleavable mutant p35 (Δp35) attenuated amyloidosis and improved cognitive function in a familial Alzheimer's disease mouse model.
Furthermore, neurons expressing T835MUNC5C are more susceptible to cell death from multiple neurotoxic stimuli, including β-amyloid (Aβ), glutamate and staurosporine.
Ori decreased the LC3-II/I ratio, p62 and cathepsin D (Ctsd) protein levels and the number of autolysosomes, whereas the protein levels of Ulk1 and Beclin-1 were no different between the control and treatment groups, indicating increased autolysosome clearance and thus a decreased Aβ burden in the brain.
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.
Consequently, miR-H1-mediated Ubr1 silencing resulted in the accumulation of β-amyloid, which might contribute to the neurodegenerative pathogenesis enhanced by HSV-1.
Here, we have investigated ubiquilin-1 expression in human brain in relation to AD-related neurofibrillary pathology and the effects of ubiquilin-1 overexpression on BACE1, tau, neuroinflammation, and neuronal viability in vitro in co-cultures of mouse embryonic primary cortical neurons and microglial cells under acute neuroinflammation as well as neuronal cell lines, and in vivo in the brain of APdE9 transgenic mice at the early phase of the development of Aβ pathology.
Neuropathological findings in cerebral B-proteinamyloidosis. Differences and similarities in those cases presenting as a cerebral hemorrhage and those presenting as a dementia of the Alzheimer type.
AmyloidB-protein/amyloid A4 is a peptide present in the neuritic plaques, neurofibrillary tangles and cerebrovascular deposits in patients with Alzheimer's disease and Down's syndrome (trisomy 21) and may be involved in the pathogenesis of Alzheimer's disease.
Some modulatory effects of TYROBP on Alzheimer's-related genes were only apparent on a background of mice with cerebral amyloidosis due to overexpression of mutant APP/PSEN1.
Importantly, we show that constitutive absence of TYROBP/DAP12 in the amyloidosis mouse model prevented appearance of the electrophysiological and learning behavior alterations associated with the phenotype of APP<sup>KM670/671NL</sup>/PSEN1<sup>Δexon9</sup> mice.
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.
The chronic accumulation of inflammatory mediator in neuronal cells facilitates interactions of TXNIP-nucleotide binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) and NLRP3-ASC, which increases β-amyloid (Aβ) secretion.
Hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) is a rare, life-threatening disease, caused by point mutations in the transthyretin gene.