Activin A protects against lipopolysaccharide/TNF-α induced damage of dopaminergic neurons both in vivo and in vitro by regulating mitochondrial fusion

Abstract

There is increasing evidence that the pathogenesis of Parkinson’s disease (PD) is closely related to mitochondrial dysfunction and iron deposition. Activin A (Act A) is a homodimeric cytokine from the TGF-β superfamily and has neuroprotective effects in various neurological diseases. However, the specific mechanisms by which Act A exerts a neuronal protective effect in PD remain unclear. In this study, we selected lipopolysaccharide (LPS) −induced PD model mice to investigate the mechanism of protective effects of Act A on neurons, focusing on its effects on the expression of mitochondrial dynamics and ferroptosis related proteins. Meanwhile, the human neuroblastoma cell line SH-SY5Y was selected in vitro to detect mitochondrial membrane potential and reactive oxygen species (ROS) levels to clarify the potential molecular mechanism of Act A in PD. The results of the study showed that Act A attenuated dopaminergic neuron damage in the LPS-induced PD model mice, possibly through regulating mitochondrial dynamics, inhibiting ferroptosis, and reducing ROS. Additionally, mitochondrial fusion inhibitor (MFI8) increased the intracellular ROS levels, while Act A attenuated MFI8-mediated ROS elevation. In conclusion, our results suggest that Act A is involved in the onset and development of PD and may exert neuronal protective effects by regulating mitochondrial fusion.