Ginsenoside Rg1 decreases neurofibrillary tangles accumulation in retina by regulating activities of neprilysin and PKA in retinal cells of AD mice model.

Neurofibrillary tangles (NFTs) are the major component of senile plaques in the brains of patients with Alzheimer's disease (AD). However, the mechanism causing NFTs accumulation in AD patients' retina is also elusive. Thus, we investigated the effects of ginsenoside Rg1 on NFTs accumulation in retinal pigment epithelial (RPE) cells isolated form double transgenic APP/PS1 mice model. NFTs amounts in culture supernatants were examined by enzyme-linked immunosorbent assay. Activity and mRNA transcription of enzymes and proteins that regulate NFTs accumulation were examined by activity assay and reverse transcription PCR. The expression of neprilysin (NEP) and neutral endopeptidase (PKA) were detected by western blot assay. Rg1 significantly decreased NFTs accumulation in isolated RPE cells. Activity of NEP was significantly increased, and activity of PKA was significantly decreased in cell lysates of Rg1-feeding APP/PS1 mice compared with non-Rg1-feeding mice. mRNA level of NEP was significantly higher and mRNA level of PKA was significantly lower in cells of Rg1-feeding mice than nonfeeding mice. The phosphorylation of tau at Thr231, Thr205, and Ser396 were significantly decreased in RPE of Rg1-feeding APP/PS1 mice compared with the non-Rg1-feeding mice. Rg1 decreased the NFTs production in RPE cell of APP/PS1 mice by modulating the expression and activity of NEP and PKA, which perform the function through downregulating the phosphorylation of tau protein.