Excess Aβ production by the key protease BACE1, results in Aβ aggregation, forming amyloid plaques, all of which contribute to the pathogenesis of Alzheimer's disease.
BACE1 was inhibited, thereby reducing amyloid plaques (Aβ) deposition and eventually reducing inflammation and apoptosis of neurons as revealed by immunohistopathological examination.
Transcript levels of the genes associated with loss of synaptic plasticity (Bdnf, Syn, GluN1, α7-nAChR, and M<sub>1</sub>-mAChR), formation of neurofibrillary tangles (Tau4 and Tau3), and amyloid plaques (App, Adam10, and Bace1), in the hippocampus of rats at 0, 1, 3, 6, and 9 days after ODX (D<sub>0</sub>, D<sub>1</sub>, D<sub>3</sub>, D<sub>6</sub> and D<sub>9</sub>, respectively) were determined.
The β-site amyloid cleavage enzyme 1 (BACE1) is the major constituent of amyloid plaques and plays a central role in this brain pathogenesis, thus it constitutes an auspicious pharmacological target for its treatment.
In APP/PS1 transgenic mice, the nanocomplexes significantly decrease BACE1 mRNA and the amyloid plaques, suppress phosphorylated tau protein levels, as well as promote hippocampal neurogenesis.
Targeting BACE1 (β-site APP cleaving enzyme 1 or β-secretase) is the focus of Alzheimer's disease (AD) research because this aspartyl protease is involved in the abnormal production of β amyloid plaques (Aβ), the hallmark of its pathophysiology.