Propofol Attenuates α-Synuclein Aggregation and Neuronal Damage in a Mouse Model of Ischemic Stroke
α-Synuclein is a soluble monomer abundant in the central nervous system. Aggregates of α-synuclein, consisting of higher-level oligomers and insoluble fibrils, have been observed in many chronic neurological diseases and are implicated in neurotoxicity and neurodegeneration. α-Synuclein has recently been shown to aggregate following acute ischemic stroke, exacerbating neuronal damage. Propofol is an intravenous anesthetic that is commonly used during intravascular embolectomy following acute ischemic stroke. While propofol has demonstrated neuroprotective properties following brain injury, the mechanism of protection in the setting of ischemic stroke is unclear. In this study, propofol administration significantly reduced the neurotoxic aggregation of α-synuclein, decreased the infarct area, and attenuated the neurological deficits after ischemic stroke in a mouse model. We then demonstrated that the propofol-induced reduction of α-synuclein aggregation was associated with increased mammalian target of rapamycin/ribosomal protein S6 kinase beta-1 signaling pathway activity and reduction of the excessive autophagy occurring after acute ischemic stroke.
KeywordsPropofol α-Synuclein Autophagy Stroke Neuroprotection
We thank Mengyao Qu and Yushang Zao for surgical assistance with the mouse stroke model. This work was supported by the National Natural Science Foundation of China (81771139) and the Beijing Natural Science Foundation (7194270).
Conflict of interest
All authors claim that there are no conflicts of interest.
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