Yerba mate extract stimulates autophagy and modulates AMPK pathway in SH-SY5Y cells: Insights into its neuroprotective potential in Parkinson’s disease.

Current treatments for Parkinson's disease (PD) are symptomatic and unable to stop neuronal death, highlighting the need for complementary strategies which may delay neurodegeneration such as dietary interventions. Yerba mate (Ilex paraguariensis, YM) has been inversely associated with the development of PD. Previously, our group demonstrated that YM enhances the survival of dopaminergic neurons in primary mesencephalic cultures. Like coffee, mate contains high amounts of Chlorogenic acid (CGA), which may modulate energy metabolism and promote neuronal survival, likely activating AMPK, a pathway involved in energy homeostasis and autophagy, a crucial process in PD pathophysiology that may clear protein aggregates associated with neurodegeneration. However, the mechanisms behind YM extract and CGAs neuroprotective effects are underexplored. Thus, in this study, we use human SH-SY5Y neuroblastoma cells to assess YM and CGAs effect on autophagy. To assess autophagic flux, we evaluated autophagy markers LC3-II levels by immunofluorescence and Western blot, and p62 levels by Western blot. Results show that YM extract increases LC3-II levels and slightly decreases p62/SQSTM1 levels, reflecting an increase in autophagic flux. Therefore, this study outlines enhanced autophagy as a potential neuroprotective mechanism that may position YM as a natural dietary candidate to counteract neurodegeneration.