Salidroside protects SH-SY5Y from pathogenic [alpha]-synuclein by promoting cell autophagy via mediation of mTOR/p70S6K signaling

The abnormal aggregation of [alpha]-synuclein ([alpha]-syn), which is an important pathological feature of Parkinson's disease (PD), is cytotoxic to dopaminergic neurons and causes cellular damage and apoptosis. Salidroside (SAL) is the main active component of the traditional Chinese medicine Rhodiola rosea. Previous research has demonstrated that SAL exerts cellular protection against cell senescence and neurodegeneration. However, the role and mechanism of action of SAL in PD remain unclear. The present study used overexpression of the wild-type and the A53T mutation of [alpha]-syn to induce a neuronal model of PD in SH-SY5Y cells, which led to neuronal toxicity and a reduced cell proliferation index. SAL increased the cell proliferation index of both PD model groups in a dose-dependent manner. Additionally, SAL alleviated pathogenic phosphorylated (Ser129) [alpha]-syn expression as well as the ratio of microtubule-associated proteins 1A/1B light chain 3 (LC3)-I to LC3-II expression, which is related to autophagic function. Furthermore, the results suggested that the underlying mechanism for the SAL-induced protection of PD model neurons may involve the preservation of autophagy, which attenuates the phosphorylation of [alpha]-syn in neurons predominantly via mTOR/p70S6K, and is independent of the PI3K/Akt signaling pathway. Key words: SAL, [alpha]-syn, PD, autophagy, mTOR