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Review
. 2023 Mar 1:17:1145318.
doi: 10.3389/fnins.2023.1145318. eCollection 2023.

Tau protein plays a role in the mechanism of cognitive disorders induced by anesthetic drugs

Zheping Chen  1 , Shenghan Wang  1 , Zhaoqian Meng  1 , Yuyang Ye  1 , Guoliang Shan  1 , Xinyue Wang  1 , Xin Zhao  1 , Yanwu Jin  1
Affiliations
Review

Tau protein plays a role in the mechanism of cognitive disorders induced by anesthetic drugs

Zheping Chen et al. Front Neurosci. .

Abstract

Cognitive disorders are mental health disorders that can affect cognitive ability. Surgery and anesthesia have been proposed to increase the incidence of cognitive dysfunction, including declines in memory, learning, attention and executive function. Tau protein is a microtubule-associated protein located in the axons of neurons and is important for microtubule assembly and stability; its biological function is mainly regulated by phosphorylation. Phosphorylated tau protein has been associated with cognitive dysfunction mediated by disrupting the stability of the microtubule structure. There is an increasing consensus that anesthetic drugs can cause cognitive impairment. Herein, we reviewed the latest literature and compared the relationship between tau protein and cognitive impairment caused by different anesthetics. Our results substantiated that tau protein phosphorylation is essential in cognitive dysfunction caused by anesthetic drugs, and the possible mechanism can be summarized as "anesthetic drugs-kinase/phosphatase-p-Tau-cognitive impairment".

Keywords: anesthetic drugs; cognitive impairment; phosphorylation; sevoflurane; tau protein.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Tau biology: isotypic expression. MAPT gene produces six tau isoforms in human central nervous system through alternative splicing. The complete tau consists of N-terminal region, proline rich domain, microtubule binding domain (MTBD) and C-terminal region. The repetitive sequence constitutes the core of microtubule binding region and the core of PHF. The alternative splicing of exons 2 and 3 determines the number of N-terminal insertion sequences composed of 29 amino acids, which can form isomers (0N, 1N and 2N) with 0 or 1 or 2 N-terminal insertion sequences. Exon 10 was selectively spliced in MTBD to produce 3R and 4R tau. The C-terminal region is common to all subtypes. The amino acid length of each tau subtype is shown on the far right. aa, amino acid.
FIGURE 2
FIGURE 2
Tau pathomechanisms. The abnormal transcription and post-translational modification of MAPT gene intertwine with each other to form NFTs. NFTs affect axonal transport, synaptic plasticity, and cytoskeleton stability of neurons. Persistent diffusion and cell to cell p-Tau spreading eventually lead to cognitive impairment.
FIGURE 3
FIGURE 3
Possible mechanism of different anesthetic drugs-induced-Tau phosphorylation at different sites. CDK5, cyclin-dependent kinase 5; GSK-3β, glycogen synthase kinase-3β; PP2A, protein phosphatase 2A; PP2B, protein phosphatase 2B; PP1, protein phosphatase 1; CDK5, cyclin-dependent kinase 5; JNK, c-Jun NH2-terminal kinas.
FIGURE 4
FIGURE 4
Anesthetic drugs-kinase/phosphatase-p-Tau-cognitive impairment. Key kinase/phosphatase includes GSK-3β, GSK-3α, CDK5, P38, JNK, PP1, PP2A, and PP2B. The phosphorylation sites of key tau include Ser199, Ser202, Ser262, Ser356, Ser396, Ser404, Thr181, Thr205, Thr217, and Thr231. The effect of anesthetic drugs on cognitive dysfunction through tau may be the result of the balance between various kinases and phosphatases. PP2A, protein phosphatase 2A; PP2B, protein phosphatase 2B; PP1, protein phosphatase 1; CDK5, cyclin-dependent kinase 5; GSK-3α, glycogen synthase kinase-3α; GSK-3β, glycogen synthase kinase-3β; JNK, c-Jun NH2-terminal kinas.
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Grants and funding

This present study was supported by grants from Shandong Provincial Natural Science Foundation (No. ZR2021MH016).

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