Regular intake of yerba mate (YM) is beneficial for Parkinson's disease (PD), including a lower prevalence of developing the disease in humans and a robust neuroprotective effect on dopaminergic neurons in vitro from our lab. Also, unpublished results show that YM activates the AMPK pathway and autophagy, which are strongly linked to cell homeostasis. The hallmark of PD is the progressive death of dopaminergic neurons, however, its cause is uncertain. In order to understand this neuroprotective effect, we aim to investigate the molecular pathways regulated by 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. Here, we aim to dissect the effect of the main active compounds present in YM, as well as other widely used beverages, such as tea and coffee. We treat SH-SY5Y cells with chlorogenic acid, theobromine, and caffeine, and we are exploring the regulation of AMPK and autophagy through qRT-PCR, western blot (WB), and histology. Our pioneering results suggest that YM regulates cell metabolism, although it is still unknown which active compounds and downstream pathways are involved. Further work is still necessary to fulfil our hypothesis, but current results help to envisage how natural compounds may modulate neuronal health and therefore impact the natural history of neurodegenerative pathologies such as Parkinson’s disease.