Ramelteon ameliorated 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity in neuronal cells in a mitochondrial-dependent pathway

ABSTRACT

Parkinson’s disease (PD) is a common neurodegenerative disease with global health and economic impact. 1-methyl-4-phenylpyridinium (MPP+)-induced mitochondrial dysfunction and oxidative stress are reported to participate in the pathological mechanism of PD. Ramelteon is a novel oral hypnotic agent that has recently been reported to display neuronal protective effects. However, it is unknown whether Ramelteon possesses a beneficial effect in PD. In this study, we aimed to examine the potential function of Ramelteon in MPP+-challenged neurons. We found that Ramelteon rescued the cell viability reduced by MPP+-stimulation. Further, oxidative stress in MPP+-challenged SH-SY5Y cells was mitigated by Ramelteon as verified by the upregulated levels of mitochondrial reactive oxygen species (ROS) and protein carboxyl, and the upregulation of NADPH oxidase 4 (NOX-4). Furthermore, the declined mitochondrial membrane potential (_ΔΨ_m) caused by MPP+ was reversed by Ramelteon. Importantly, Ramelteon attenuated MPP+-induced apoptosis, accompanied by a decreased ratio of Bax/Bcl-2, inhibition of cytochrome C release, and downregulation of cleaved caspase-3. For the first time, we conclude that Ramelteon might ameliorate MPP+-induced neurotoxicity in neuronal cells in a mitochondrial-dependent pathway.

KEYWORDS:

• Parkinson’s disease
• mpp+
• mitochondria
• ramelteon

Acknowledgements

This study is supported by “Guangzhou Medical University”.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Chuo Li contributed to the experiment design; Chuo Li, Yusheng Zhang, Rongrong Liu, and Yuzhen Mai performed the experiments and analyzed the data; Chuo Li drafted the manuscript.

Additional information

Funding

This study was supported by the Natural Science Foundation of China (81200903).