Abstract
Alzheimer's disease (AD) is a complex neurodegenerative disease that is prevalent around the world. Both Apelin-13 and proliferator-activated receptor-γ (PPARγ)/PPARγ co-activator 1α (PGC-1α) are regarded as candidate targets for treating AD. The investigation examined whether Apelin-13 exerts neuroprotective effects via PGC-1α/PPARγ signaling. In this study, Apelin-13 improved cognitive deficits in AD mice, while SR-18,292 (a PGC-1α inhibitor) interfered with the therapeutic effects of Apelin-13. Mechanistically, Apelin-13, PGC-1α and PPARγ were decreased in AD mice and oxygen-glucose deprivation (OGD)-induced neuronal cells. Apelin-13 bound to PGC-1α and negatively regulated the expression of PGC-1α and PPARγ. In turn, PGC-1α accelerated the accumulation of Apelin-13 and PPARγ. Additionally, neuronal apoptosis was inhibited, and the abundance of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase 3) was induced. The content of reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) fluctuated. The level of inflammatory factors (interleukin-6, IL-6, IL-10, tumor necrosis factor-α, TNF-α) was regulated. In short, Apelin-13 exerted anti-apoptosis, anti-oxidant stress and anti-inflammatory effects. Interestingly, PGC-1α silencing promoted neuronal apoptosis, oxidant stress and inflammation, and overexpression of PGC-1α exhibited the opposite. More importantly, inhibition of PGC-1α attenuated Apelin-13-enhanced cognitive impairment and neuronal damage. Therefore, our findings suggested that Apelin-13 exerted neuroprotective effects in part via the PGC-1α/PPARγ pathway.