Our previous study showed that the expression level of miR-409-5p was stably downregulated in the early stage of APP/PS1 double transgenic mice model of AD.
Moreover, analysis of gene ontology in the AD brain revealed that important signaling pathways and processes related to AD pathogenesis such as translational regulation, oxidative stress, cytoskeleton reorganization, and small GTPase signal transduction were altered in APP/PS1 Tg/sEH<sup>-/-</sup> mice compared with APP/PS1 Tg mice.
A neuropathologic hallmark of Alzheimer's disease (AD) is the presence of senile plaques that contain neurotoxic amyloid-β protein (Aβ) species, which are generated by the cleavage of APP by secretases such as the γ-secretase complex, preferentially located in detergent-resistant membrane (DRM) regions and comprising endoproteolysed amino- and carboxyterminal fragments of presenilin, nicastrin, anterior pharynx defective 1, and presenilin enhancer 2.
Taken together, our data showed that mAb A8 is highly efficacious in APP/PS1 mice as a treatment for AD, and the underlying mechanism may target synaptic pathology by inhibiting the amyloid cascade.
We recently demonstrated an endolysosomal accumulation of the β-secretase-derived APP C-terminal fragment (CTF) C99 in brains of Alzheimer disease (AD) mouse models.
We investigated the beneficial effects of active compounds of Epimedium, Astragaoside and Puerarin on iron metabolism in the frontal cortex of six-month-old APPswe/PS1<sub>ΔE9</sub> (APP/PS1) double transgenic mouse, a model of AD.
We applied the approach to the exploration of ligands for β-site amyloid precursor protein [APP]-cleaving enzyme 1 (BACE1), a major target for Alzheimer Disease (AD), with less off-target effect toward cathepsin D. We demonstrated that the density region of BACE1 and cathepsin D ligands are well-divided, and a group of natural compounds as a target for exploration of new drug candidates also has significantly different distribution on the density map.
Based on the amyloid cascade hypothesis, the main component of senile plaques, the amyloid-beta (Aβ) peptide, and its derivative called amyloid precursor protein (APP) both have been found to place their central roles in AD development for years.
GPR40 agonist GW9508 and antagonist GW1100 were respectively given by i.c.v. injection to activate/inhibit the GPR40 in the brain of APP/PS1 mice which illustrated the function and mechanism of GPR40 in ameliorating AD symptoms.
Proteolysis of Amyloid Precursor Protein, APP, results in the formation of amyloid β (Aβ) peptides, which have been associated with Alzheimer's disease (AD).
Here, we used a transgenic mouse model of AD that expresses a mutant amyloid-β precursor protein (T41 mice) to investigate the effects of dactolisib (alternative name: NVP-BEZ235, abbreviation BEZ), a dual PI3K/mTOR inhibitor.
The present research work primarily investigated whether spinosin has the potential of improving the pathogenesis of Alzheimer's disease (AD) driven by β-amyloid (Aβ) overproduction through impacting the procession of amyloid precursor protein (APP).
Ras-related C3 botulinum toxin substrate 1 (Rac1), a member of the Rho-GTPase family of proteins, could be an Alzheimer's disease (AD) triggering co-factor due to its effect on both amyloid precursor protein (APP) and tau.
The data suggest that these purinergic receptors participate in the deleterious cellular and molecular effects of SOAβ that lead to the pathogenesis of AD.
AHI1 facilitates intracellular amyloid precursor protein (APP) translocation to inhibit amyloidogenic pathology of AD, and thus may be an AD biomarker.
In this study, we tested if local protein synthesis at synapses is deregulated in the brains of TgCRND8 mice, an animal model for Alzheimer's disease (AD) overexpressing mutant human amyloid precursor protein (APP).
Understanding the contribution of APP for normal functions of the nervous system is of high importance, both from a basic science perspective and also as a basis for generating new pathophysiological concepts and therapeutic approaches in AD.
Activated AEP cleaves both APP and Tau at APP N585 and Tau N368 sites, respectively, which mediate AD pathogenesis by promoting Aβ production and Tau hyperphosphorylation and inducing neuroinflammation and neurotoxicity.
Here, we investigated the roles of NDRG2 in the development of memory impairment in AD using mouse models established by amyloid β injection or crossing of APP/PS1 mice.
Our findings suggest that aberrant autophagy is not only a consequence of abnormal APP activity, but also contributes to dysregulated APP metabolism and subsequent AD pathogenesis.