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胆固醇是否是自闭症谱系障碍中异常跨膜信号的关键?

Is cholesterol both the lock and key to abnormal transmembrane signals in Autism Spectrum Disorder?

机构信息

Division of Molecular Medicine, Research Institute, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON, M5G 0A4, Canada.

Departments of Biochemistry and Laboratory Medicine & Pathobiology, University of Toronto, Ontario, M5S 1A8, Canada.

出版信息

Lipids Health Dis. 2024 Apr 20;23(1):114. doi: 10.1186/s12944-024-02075-3.

Abstract

Disturbances in cholesterol homeostasis have been associated with ASD. Lipid rafts are central in many transmembrane signaling pathways (including mTOR) and changes in raft cholesterol content affect their order function. Cholesterol levels are controlled by several mechanisms, including endoplasmic reticulum associated degradation (ERAD) of the rate limiting HMGCoA reductase. A new approach to increase cholesterol via temporary ERAD blockade using a benign bacterial toxin-derived competitor for the ERAD translocon is suggested.A new lock and key model for cholesterol/lipid raft dependent signaling is proposed in which the rafts provide both the afferent and efferent 'tumblers' across the membrane to allow 'lock and key' receptor transmembrane signals.

摘要

胆固醇稳态紊乱与 ASD 有关。脂筏在许多跨膜信号通路(包括 mTOR)中起核心作用,筏内胆固醇含量的变化会影响其有序功能。胆固醇水平受多种机制控制,包括限速酶 HMGCoA 还原酶的内质网相关降解(ERAD)。有人提出了一种通过使用良性细菌毒素衍生的 ERAD 易位蛋白竞争物来暂时阻断 ERAD 以增加胆固醇的新方法。提出了一个新的胆固醇/脂筏依赖性信号的锁钥模型,其中脂筏为跨膜提供了“锁”和“钥匙”受体跨膜信号的顺式和反式“弹子”。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2450/11032007/81d24e5994c6/12944_2024_2075_Fig1_HTML.jpg

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