**5. Conclusions**

Fucoidan is a kind of sulfated polysaccharide extracted from brown algae. UF is a heteropolysaccharide purified from fucoidan. In our previous study, we found UF had excellent neuron protective activity. However, the mechanism is still unknown. In our present study, we demonstrated that UF could act on the extracellular growth factor NGF and cause progressive activation of the PI3K–Akt pathway. Furthermore, this study provides further insight into the mechanisms of UF, including regulating downstream signaling molecules and proteins of the PI3K–Akt pathway and the a alleviate e ffect by adding LY294002, which means the neuron protective activity of UF was partly through PI3K–Akt pathway. These findings contribute to a better understanding of the critical roles of UF in treating PD and may elucidate the molecular mechanisms of UF e ffects in PD.

**Author Contributions:** Conceptualization, H.L.; formal analysis, N.W.; funding acquisition, J.W.; investigation, Jing Wang; methodology, H.L., L.G. and Y.Y.; project administration, Q.Z.; supervision, N.W. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was funded by the National Key research and Development Program of China (Grant No. 2018YFD0901104, 2019YFD0900705), Major Scientific & Engineering Projects of Innovation in Shandong Province (Grant No.2019JZZY010818), Shandong Provincial Natural Science Foundation (Grant No.ZR2019BD053), the Youth Innovation Promotion Association of CAS under Grant (No. 2016190), the Science and Technology project of Fujian Province (No. 2017T3015).

**Acknowledgments:** We thank the students Zhenzhen Deng and Yue Jin for their help with the experiment.

**Conflicts of Interest:** The authors declare no conflict of interest.
