Mitochondrial dysfunction is a key element in the progression of Parkinson’s disease (PD). The inefficient operation of the electron transport chain (ETC) impairs energy production and enhances the generation of oxidative stress contributing to the loss of dopaminergic cells in the brain. ATPase inhibitory factor 1 (IF1) is a regulator of mitochondrial energy metabolism. IF1 binds directly to the F1Fo ATP synthase and prevents ATP wasting during compromised energy metabolism. In this study, we found treatment with IF1 protects mitochondria against PD-like insult in vitro. SH-SY5Y cells treated with IF1 were resistant to loss of ATP and mitochondrial inner membrane potential during challenge with rotenone, an inhibitor of complex I in the ETC. We further demonstrated that treatment with IF1 reversed rotenone-induced superoxide production in mitochondria and peroxide accumulation in whole cells. Ultimately, IF1 decreased protein levels of pro-apoptotic Bax, cleaved caspase-3, and cleaved PARP, rescuing SH-SY5Y cells from rotenone-mediated apoptotic death. Administration of IF1 significantly improved the results of pole and hanging tests performed by PD mice expressing human α-synuclein. This indicates that IF1 mitigates PD-associated motor deficit. Together, these findings suggest that IF1 exhibits a neuroprotective effect preventing mitochondrial dysfunction in PD pathology.

While biglycan (BGN) is suggested to direct diverse signaling cascades, the effects of soluble BGN as a ligand on metabolic traits have not been studied. Herein, we tested the effects of BGN on obesity in high-fat diet (HFD)-induced obese animals and glucose metabolism, with the underlying mechanism responsible for observed effects in vitro. Our results showed that BGN administration (1 mg/kg body weight, intraperitoneally) significantly prevented HFD-induced obesity, and this was mainly attributed to reduced food intake. Also, intracerebroventricular injection of BGN reduced food intake and body weight. The underlying mechanism includes modulation of neuropeptides gene expression involved in appetite in the hypothalamus in vitro and in vivo. In addition, BGN regulates glucose metabolism as shown by improved glucose tolerance in mice as well as AMPK/AKT dual pathway-driven enhanced glucose uptake and GLUT4 translocation in L6 myoblast cells. In conclusion, our 2 of 14 | CHUNG et al.

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