ST09, a Novel Thioester Derivative of Tacrine, Alleviates Cognitive Deficits and Enhances Glucose Metabolism in Vascular Dementia Rats

CNS Neuroscience & Therapeutics
Jian-Min LiuJian-Guo Chen

Abstract

Chemical entities containing mercapto group have been increasingly attractive in the therapy of central nerve system (CNS) diseases. In the recent study, we screened a series of mercapto-tacrine derivatives with synergistic neuropharmacological profiles in vitro. We investigated the effect and mechanism of ST09, a thioester derivative of tacrine containing a potential mercapto group, on the vascular dementia (VaD) model of rat induced by bilateral common carotid arteries occlusion (2-VO). ST09 and its active metabolite ST10 retained excellent inhibition on acetylcholinesterase (AChE) activity. ST09 significantly attenuated the 2-VO-induced impairment in spatial acquisition performance and inhibited the 2-VO-induced rise of AChE activity. In the VaD model, ST09 attenuated the oxidative stress and decreased the apoptosis in the cortex and hippocampus. Compared with donepezil, ST09 exhibited a better effect on the regeneration of free thiols in 2-VO rats. Interestingly, ST09, not donepezil, greatly improved glucose metabolism in various brain regions of 2-VO rats using functional imaging of (18) F-labeled fluoro-deoxyglucose (FDG) positron emission tomography (PET). ST09 may serve as a more promising agent for the therapy of VaD t...Continue Reading

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Feb 4, 2021·Aging and Disease·Huang KuangShu-Long Yang
Aug 6, 2021·BioMed Research International·Yao XiaoWei Shen

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