化学
谷氨酸受体
抑制性突触后电位
生物化学
三羧酸
巴比妥酸
药理学
柠檬酸循环
神经科学
生物
新陈代谢
受体
作者
Xuan Ma,Kaixin Liu,Yiman Han,Yongping Bai,Fukui Shen,Mukuo Wang,Wei Wei,Jianfeng Qin,Erhong Hao,Xiaotao Hou,Yuanyuan Hou,Gang Bai
标识
DOI:10.1002/mnfr.202100963
摘要
Glutamate (Glu) and γ-aminobutyric acid (GABA) are the major excitatory and inhibitory neurotransmitters that control information flow in the brain. GABA dysfunction is a general vulnerability factor for mental illness. Cinnamaldehyde (CA) is found to have sedation in a mental illness model. However, the specific targets and molecular mechanisms related to the sedative effects of CA have not been elucidated.Metabolomics analysis and target fishing showed CA could increase the expression of GABA in vivo, and α-enolase (ENO1) is the primary target protein of CA associated with sedation. CA mainly binds with ENO1 in the cerebellar granular layer of brain, which influences the first transformations of the input signals arriving in the cerebellar cortex. The α,β-unsaturated aldehyde group of CA blocks the hydroxy group of Ser40, which induces a loss in ENO1 activation. CA also disturbs the glycolysis pathway and influences the tricarboxylic acid cycle and oxidative phosphorylation, which activate gluconeogenesis to provide energy to the brain. This mechanism is verified in zebrafish with ENO1 or glutamic acid decarboxylase (GAD) deficiency.CA demonstrates sedation and alleviates GABA dysfunction via covalent binding ENO1, which shows the potential to improve the therapy of mental illness.
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