Dopaminergic neurons show increased low-molecular-mass protein 7 activity induced by 6-hydroxydopamine in vitro and in vivo

Abstract

Background: Abnormal expression of major histocompatibility complex class I (MHC-I) is increased in dopaminergic (DA) neurons in the substantia nigra (SN) in Parkinson's disease (PD). Low-molecular-mass protein 7 (β5i) is a proteolytic subunit of the immunoproteasome that regulates protein degradation and the MHC pathway in immune cells. Methods: In this study, we investigated the role of β5i in DA neurons using a 6-hydroxydopamine (6-OHDA) model in vitro and vivo. Results: We showed that 6-OHDA upregulated β5i expression in DA neurons in a concentration- and time-dependent manner. Inhibition and downregulation of β5i induced the expression of glucose-regulated protein (Bip) and exacerbated 6-OHDA neurotoxicity in DA neurons. The inhibition of β5i further promoted the activation of Caspase 3-related pathways induced by 6-OHDA. β5i also activated transporter associated with antigen processing 1 (TAP1) and promoted MHC-I expression on DA neurons. Conclusion: Taken together, our data suggest that β5i is activated in DA neurons under 6-OHDA treatment and may play a neuroprotective role in PD.