Amyloid precursor protein (APP) proteolysis is essential for the production of β-amyloid peptides (Aβ) that form senile plaques in Alzheimer's disease (AD) brains.
In this study, we evaluated the effects of enriched environment (EE) stimulation on spatial memory and senile plaque formation in transgenic mice PDGFB-APPSwInd (TG) that overexpress the human amyloid precursor protein, normally resulting in an increased density of senile plaques.
We found that oral treatment with FLDK reversed learning and memory impairment, reduced Aβ burden and expression of β-site amyloid precursor protein cleavage enzyme 1 (BACE1), and decreased microglial activation in senile plaques.
The senile plaques (SPs) in the brain are one of the most pathophysiological characteristics of cognitive dysfunction and its major constituent amyloid β (Aβ) released from amyloid precursor protein (APP) by β (BACE1) and γ (presenilin 1) secretases .
γ-Secretase has been a therapeutical target for its key role in cleaving APP to generate β-amyloid (Aβ), the primary constituents of senile plaques and a hallmark of Alzheimer's disease (AD) pathology.
Honokiol significantly lowered A<i>β</i> production and senile plaque deposition by downregulating <i>β</i>-site amyloid precursor protein cleavage enzyme 1 and enhancing A<i>β</i> phagocytosis by microglia.
Here we show that the C/EBPβ/δ-secretase axis is activated in an age-dependent manner in different brain regions of the 3×Tg AD mouse model, elevating δ-secretase-truncated APP and Tau proteolytic truncates and promoting senile plaques and NFT formation in the brain, associated with gradual neuronal loss and chronic neuroinflammation.
δ-Secretase, an age-dependent asparagine protease, cleaves both amyloid precursor protein (APP) and Tau and is required for amyloid plaque and neurofibrillary tangle pathologies in Alzheimer's disease (AD).
Furthermore, administration of THA effectively improved the learning ability of APP/PS1 transgenic mice, and markedly reduced the number of senile plaques in their hippocampus and cortex.
Alzheimer's disease (AD) is a degenerative disorder typified by progressive deterioration of memory and the appearance of β-amyloid peptide (Aβ)-rich senile plaques.
The neuropathology of Alzheimer's disease (AD) is characterized by the widespread accumulation of neuritic plaques and neurofibrillary tangles composed of deposits of beta-amyloid peptide (Aβ) and abnormally phosphorylated tau protein (phospho-tau) respectively.
We found that Zn<sup>2+</sup> induces APP-C99 dimerization, which prevents its cleavage by γ-secretase and Aβ production, with an IC<sub>50</sub> value of 15 μm Importantly, at this concentration, Zn<sup>2+</sup> also drastically raised the production of the aggregation-prone Aβ43 found in the senile plaques of AD brains and elevated the Aβ43:Aβ40 ratio, a promising biomarker for neurotoxicity and AD.
Amyloidogenic processing of APP by β- and γ-secretases leads to the generation of amyloid-β peptide (Aβ), and the accumulation of Aβ in senile plaques is a hallmark of Alzheimer's disease (AD).
In the amyloidogenic pathway associated with Alzheimer disease (AD), the amyloid precursor protein (APP) is cleaved by β-secretase to generate a 99-aa C-terminal fragment (C99) that is then cleaved by γ-secretase to generate the β-amyloid (Aβ) found in senile plaques.
BJJS-treated APP/PS1 mice appeared to have reductions of Aβ deposition and senile plaques, and showed higher levels of neurotrophic factors in the brain.