Objective: To investigate the molecular pathways regulated by yerba mate [YM] extract and its main active compounds in a neuronal cell line as a cue to understand the cellular changes that could mediate YM-induced neuroprotection.

Background: Two epidemiological studies from non-related centres showed that consumption of YM is inversely associated with incidence of PD [1,2]. In addition, our laboratory demonstrated neuroprotection of primary dopaminergic neurons in culture [3].

Method: We explored the potential regulation of the AMPK signaling upon exposition of YM on SH-SY5Y neuroblastoma cells and studied cell growth, differentiation, and regulation of key molecular markers of cell metabolism and autophagy (AMPK, p70S6K, ULK1 & ULK3, among others) either by qRT-PCR, western blot (WB) and histology.

Results: We determined protein levels and phosphorylated status of the selected molecules. We found that YM regulates these markers in a different manner, but remarkably activating AMPK, thus providing first insights about the mechanisms that may be triggered within neurons.

Conclusion: Our pioneering in vitro results suggest that YM regulates cell metabolism despite it is still unknown the downstream pathways involved.  These results provide insights to understand how YM may modulate neuronal homeostasis. Further work is still necessary to fulfil our hypothesis, but current results help to envisage how natural compounds may modulate neuronal health and therefore impacting in the natural history of neurodegenerative pathologies such as Parkinson’s Disease.

References: 1 – Bernardi A, Ballestero P, Schenk M, Ferrario M, Gómez G, Rivero R, Avale E, Taravini I, Gershanik O, Guerrero S, Ferrario JE. Yerba mate (Ilex paraguariensis) favors survival and growth of dopaminergic neurons in culture. Mov Disord. 2019 Jun;34(6):920-922. doi: 10.1002/mds.27667.

2 – Gatto EM, Melcon C, Parisi VL, Bartoloni L, Gonzalez CD. Inverse association between yerba mate consumption and idiopathic Parkinson’s disease. A case-control study. J Neurol Sci. 2015 Sep 15;356(1-2):163-7. doi: 10.1016/j.jns.2015.06.043.

3 – Medeiros MS, Schumacher-Schuh AF, Altmann V, Rieder CRM. A Case-Control Study of the Effects of Chimarrão (Ilex paraguariensis) and Coffee on Parkinson’s Disease
Front Neurol. 2021 Mar 10;12:619535. doi: 10.3389/fneur.2021.619535. eCollection 2021.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/ilex-paraguariensis-yerba-mate-modulates-the-ampk-pathway-and-downstream-key-metabolic-mechanism-that-may-explain-its-neuroprotective-role/