Parkinson's disease (PD) is progressive neurodegenerative disease characterized by the selective loss of dopaminergic neurons and accumulation of α-synuclein in the substantia nigra. Neurotoxins, such as rotenone and 6-hydroxidopamine are widely used to induce in vitro model of PD. These neurotoxins induce mitochondrial dysfunction and increase oxidative stress, leading to neuronal degeneration and cell death by apoptosis. Dehydroepiandrosterone (DHEA) and its sulfate (DHEAS), along with brain-derived neurotrophic factor (BDNF) are involved in neuroprotection. Levels of both DHEA(S) and BDNF decrease with age and play important role in brain aging and neurodegeneration. Therefore, understanding the mechanisms involved in neurodegeneration is the key to identifying potential therapeutic strategies for PD. Potential mechanism of neuroprotective effects of DHEA(S) could involve BDNF and the PI3K-AKT signaling pathway. The objective of this study was to investigate the protective effects of DHEA(S) and BDNF in promoting cell survival in an in vitro model of PD. Neuroblastoma SH-SY5Y cells and dopaminergic N27 cells were pre-treated with DHEA(S) and BDNF, and after 24h cells were injured with rotenone or 6-hydroxidopamine. Alterations in cell viability were analyzed using the MTT test and the number of apoptotic and necrotic cells was determined using Hoechst 33342 and Propidium Iodide. Real Time PCR and Western Blot were used to determine expression of proteins involved in apoptosis and BDNF signaling. Analyzing the expression of apoptotic markers, such as BAX and BCL2, and targeting the PI3K-AKT signaling pathway, could provide us with a better understanding of the molecular mechanisms underlying the pathophysiology of PD.