Objective: To investigate the level of serum response factor(SRF) in rotenone-induced Parkinson’s disease(PD) model and PD patients, and explore the potential protective role and underlying mechanisms of SRF in PD.

Background: SRF is a highly expressed translation factor in neurons. It was recently reported that SRF plays a critical role in neuronal survival and has been considered to involve some neurodegenerative disease. Previous studies suggest that ablation of SRF causes exacerbated sensitivity of DA neurons to MPTP.

Methods: Transient transfection has been used to knock down or overexpress SRF. CCK 8 was performed to detect the cell viability. Immunohistochemistry and Western Blot were emploied to evaluate the dynamic expression level of SRF in rotenone-treated PD molde in vivo. The consequence change of the knock down and overexpression of SRF were comfired by Western blot and rtPCR.The Reporter luciferase activity was assessed using a luciferase assay kit. ELISA was used to examed the level of SRF in the serum of PD patients and normal people.

Results: We find a time-dependent decrease of SRF in rotenone-treated PD molde in vivo and in vitro, as well as in the serum of PD patients. In addition, a commensurate loss of TH, Beclin 1, LC3-II, P62 were detected in Lewis rats treated with rotenone. The low expression of SRF leads to increased sensitive to neurotoxin rotenone in PC12 cells. Conversely, SRF overexpression rescues the injure. While The protective effect of SRF is eliminated when the Atg5 were knocked down. The same outcome were observed in Beclin 1-knockdown cells. More importantly, the reporter luciferase assay illustrated an elevation of Beclin 1 promoter activity when SRF were overexpressed. In the end, we detected a decreased autophagic activity and the accumulation of α-Synuclein in PD model, when SRF were absent.

Conclusions: Our data shows that there is a dynamic decrease of SRF in PD pathological processes. SRF decrease the susceptibility to rotenone in dopaminergic PC12 cells, and SRF protect PC12 cells against rotenone by regulate Autophagosome-Lysosome pathway(ALP), furthermore by binding to the promoter of Beclin 1, which is a critical regulator of ALP. Moreover, SRF enhance the degradation of α-Synuclein through the ALP.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-serum-response-factor-srf-protect-dopamine-da-neurons-in-parkinsons-disease-partially-by-mediate-autophagy-through-a-beclin-1-dependent-pathway/