miR-124 downregulates BACE 1 and alters autophagy in APP/PS1 transgenic mice

Abstract

One role of BACE 1 (Beta-site amyloid precursor protein cleaving enzyme 1) is to cleave the sequential amyloid precursor protein (APP) into β-Amyloid (Aβ), the accumulation of which is an important participant in the formation of the amyloid plaques and neurofibrillary tangles of Alzheimer's disease (AD). Our previous study showed BACE 1, the potential functional downstream target of miR-124, to be connected to cell death in AD cell models. Recent studies have shown that autophagy is altered in AD, however, as to whether miR-124 is involved in this alteration is not clear. In this study, 7-month-old APP/PS1 transgenic mice were transfected with miR-124 lentiviral vectors, injected bilaterally into the dentate gyrus (DG) of mice hippocampi. Following 7 days of recovery, both behavior and biochemical pathology tests were implemented. The results demonstrated learning ability improvement and specific AD pathology alleviation. Meanwhile there was down-regulation of Bcl-2 to Bax ratio expression, increase in Beclin-1 and decreases in expression of LC3II, Atg5 and p62/SQSTMl. In view of this, we hypothesis that miR-124 conducts its neuroprotective effect through BACE 1 by regulation of autophagic pathways.

Keywords: APP/PS1 transgenic mice; Alzheimer’s disease; Autophagy; BACE 1; miR-124.