**5. Conclusions**

*GPC* proved safe for mice during almost life-long supplementation starting from an early age. The long-term *GPC* feeding did not produce any visible harmful effects on the general condition of the animals, nor disturbed their behavioral performance or cognitive function. Hence, such treatment seems to be applicable as a preventive long-term intervention at the asymptomatic preclinical and early stages of neurodegenerative diseases. *GPC* affected the cognitive function in transgenic PD mice by modulating their memory-specifically, by enhancing memory reconsolidation and abating memory extinction. The behavioral and cognitive effects of *GPC* were accompanied by a reduction in α-synuclein accumulation in the frontal cortex and neuroinflammatory response in the frontal cortex and hippocampus. Our findings confirmed the neuroprotective activity of grape polyphenols against α-synuclein in vivo. Thus, a diet supplemented with grape polyphenol concentrate is suggested as promising functional nutrition for aging people and patients with neurodegenerative disorders, especially Parkinson's disease.

**Supplementary Materials:** The following are available online at Figure S1: Effects of the overexpression of A53T-mutant α-synuclein and dietary supplementation with *GPC* for four months on the immunoreactivity against the IBA1 microglial marker or CD54 inflammatory marker in the hippocampal CA1 area, CA3 area, and dentate gyrus (DG) in mice, Table S1: Content (mg/L) of active polyphenols in the grape concentrate *Enoant* (*GPC*) and dry wine material (DWM) from Vitis vinifera L. cv. 'Cabernet Sauvignon' according to Zaitsev et al. (2010).

**Author Contributions:** Conceptualization, M.A.T., T.G.A., E.K.K.; methodology, M.A.T., T.G.A.; validation, M.V.T., N.I.D.; investigation, M.V.O., A.A.A.; writing—original draft preparation, M.A.T., N.G.T., E.K.K.; writing—review and editing, M.A.T., N.G.T., E.K.K.; visualization, M.A.T.; supervision E.K.K.; project administration, E.K.K. All authors have read and agreed to the published version of the manuscript.

**Funding:** The work was supported by Russian Science Foundation (grant No. 16-14-00086).

**Acknowledgments:** We thank Konstantin S. Pavlov for technical support in animal treatment and behavioral testing. The studies were implemented using the equipment of the Federal State Budgetary Scientific Institution "Scientific Research Institute of Neurosciences and Medicine" (theme No. AAAA-A16-116021010228-0).

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