In addition, we also elaborated the role of circulating lncRNA major including beta-site APP cleaving enzyme 1 (BACE1) and its antisense lncRNA BACE1-AS in AD pathological advancement.
β-secretase (BACE1) and its naturally occurring anti-sense RNA (BACE1-AS) have established role in the pathologic process leading to Alzheimer's disease.
We defined enzymatic activity attributable specifically to BACE1 as the activity that was blocked by the specific inhibitors, which is still higher in AD subjects.
It was demonstrated that lncRNA BACE1-AS expression was highly expressed in blood samples from AD patients, and also upregulated in peripheral blood samples and hippocampi from an AD animal model.
In an obese mouse model, a high-fat diet (HFD) significantly increased the expression levels of APP and BACE1 as well as the AD pathology in the mouse brain.
Downregulation of lncRNA BACE1‑AS expression in SH‑SY5Y cells by siRNA silencing resulted in the attenuation of the ability of BACE1 to cleave APP and delayed the induction of SP formation in the SP AD SH‑SY5Y cell model.
In this review we present current knowledge on BACE1, discussing its structure, function and complex regulation with a view to understanding BACE1 function in the brain, and BACE1 as a target in blocking aberrant Abeta production in AD.
Peroxisome proliferator-activated receptor gamma (PPARgamma) regulates the transcription of BACE1 as well as inflammatory responses in the brain and atherosclerotic risk factors known to be involved also in AD.