Roger Alleviates Memory Impairment in a Rat Model of Alzheimer's Disease Through the EGR1/BACE1/APP Axis.

Memory deficits and loss are the earliest and most prominent features of Alzheimer's disease (AD). This study was aimed to clarify the mechanistic basis of an active fraction of Roger (AFPR) on the memory abilities of AD rat models, which involves early growth response 1 (EGR1) expression and β-secretase 1 (BACE1)-mediated deposition of amyloid β peptide (Aβ). An AD rat model was developed by Aβ25-35, which was further treated with AFPR alone or in combination with lentiviral EGR1. The Morris water maze test and HE and Fluoro-Jade C staining were adopted to observe the memory behaviors, hippocampus neuron morphology, and Aβ deposition. Aβ25-35-induced SK-N-SH and HT22 neurons were subjected to AFPR for experiments on neuronal viability and apoptosis. AFPR improved the impaired memory function, preserved the neuron structure, and suppressed Aβ deposition in AD rat models. Further, the expression of APP pathway-related proteins was downregulated by AFPR in both rat and cellular models. Moreover, AFPR inhibited the Aβ25-35-induced neuronal apoptosis. AFPR suppressed the expression of EGR1, downregulated the BACE1 expression impeding the binding of EGR1 to the BACE1 promoter, and thus blocked the activation of the APP signaling, ultimately protecting neurons. Notably, the aforementioned effects of AFPR were in a concentration-dependent manner; among three doses, 3.65, 15.6, and 30 mg/(kg·d), high-dose AFPR exhibited the most appreciable effects. In conclusion, AFPR inhibited the BACE1 expression by repressing the binding of EGR1 to the promoter of BACE1, thereby suppressing the Aβ deposition and improving the memory function of AD rats.