Investigation of the effects of mitochondria-targeted therapy on 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells
Project no. 28449 · Status: Kapanmış (Yayın bekleniyor) · 2023
Summary
<p>Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized not only by motor symptoms but also by a range of non-motor manifestations. Its complex pathogenesis involves dopaminergic neuronal loss, mitochondrial dysfunction, oxidative stress, apoptosis, and inflammation. In this study, the protective effects of two mitochondria-targeted antioxidant agents, MitoQuinone (MitoQ) and MitoTEMPO, were evaluated in an SH-SY5Y neuroblastoma cell model of PD induced by 6-hydroxydopamine (6-OHDA). The cells were pretreated with MitoQ and/or MitoTEMPO for 24 hours, followed by exposure to 100 µM 6-OHDA for another 24 hours. Cell viability was assessed via the MTS-PMS assay, long-term proliferative capacity via colony formation assay, apoptosis levels via Hoechst 33258 staining and caspase-3 ELISA, and molecular pathways via Western blot analysis.</p><p>Results demonstrated that MitoTEMPO at 1, 10, and 100 µM and MitoQ at 50 and 100 nM significantly preserved cell viability under 6-OHDA-induced stress. Combination therapies revealed a synergistic protective effect. Colony formation data indicated that MitoTEMPO provided superior long-term proliferative support. Western blot analyses revealed decreased expression of pro-apoptotic Bax and increased levels of anti-apoptotic Bcl-2 and anti-ferroptotic GPX4. Additionally, increased Beclin-1 levels suggested the activation of autophagy pathways.</p><p>These findings highlight that mitochondria-targeted redox modulators, such as MitoQ and MitoTEMPO, can mitigate 6-OHDA-induced neurotoxicity by modulating multiple cell death pathways, including apoptosis, autophagy, and ferroptosis. The combination of both agents may further enhance neuroprotection via complementary mechanisms. This in vitro evidence provides a strong rationale for future in vivo and translational studies focusing on multi-targeted antioxidant strategies in Parkinson’s disease and related neurodegenerative conditions.</p>