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Abstract: In this work non polar (hexane) and polar (methanol and hot water) extracts of cork oak (Quercus suber) and holm oak (Quercus ilex) acorns were evaluated for the first time for in vitro neuroprotective properties, by determining their in vitro inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) and their capacity to attenuate hydrogen peroxide-induced injury in the human dopaminergic cell line SH-SY5Y. Total content of phenolics, tannins and flavonoids, HPLC profile of the main phenolic compounds and antioxidant activity were also determined. The methanol extracts showed inhibitory activities against AChE and BChE. The best results toward AChE were obtained with cork oak extract (69.4% inhibition at the concentration of 1mg/ml), while for BChE the highest inhibition (46% inhibition at the concentration of 1mg/ml) was obtained with holm oak. Moreover, methanol extracts were able to prevent oxidative stress-induced cytotoxicity in SH-S5SY cells. The methanol extract of holm oak exhibited the highest RSA, with values of 63.8% and 49.7% on DPPH and ABTS radicals at the concentration of 1mg/ml, respectively. In general the extracts exhibited no reducing potential. The methanol extract from cork oak acorns had the highest content in phenolic compounds (25.2mg GAE/g, DW), while the water extracts had the maximum level of flavonoids (1.7mg RE/g, DW). Tannins were present in higher amounts in the water extract of holm oak (91.6CE/g, DW). The main compounds in the methanol extract from holm oak acorns were (−)-epicatechin and catechol, while gallic acid and (+)-catechin were the main constituents of the methanol extract from cork oak acorns. Our results indicate that cork and holm oak acorns provide a valuable source of biomolecules useful for alleviating symptoms associated with Alzheimer''s disease and other neurodegenerative ailments. [Copyright &y& Elsevier]