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肌醇生物合成的调控:平衡健康与病理生理

Regulation of Inositol Biosynthesis: Balancing Health and Pathophysiology.

作者信息

Case Kendall C, Salsaa Michael, Yu Wenxi, Greenberg Miriam L

机构信息

Department of Biological Sciences, Wayne State University, Detroit, MI, USA.

Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USA.

出版信息

Handb Exp Pharmacol. 2020;259:221-260. doi: 10.1007/164_2018_181.

Abstract

Inositol is the precursor for all inositol compounds and is essential for viability of eukaryotic cells. Numerous cellular processes and signaling functions are dependent on inositol compounds, and perturbation of their synthesis leads to a wide range of human diseases. Although considerable research has been directed at understanding the function of inositol compounds, especially phosphoinositides and inositol phosphates, a focus on regulatory and homeostatic mechanisms controlling inositol biosynthesis has been largely neglected. Consequently, little is known about how synthesis of inositol is regulated in human cells. Identifying physiological regulators of inositol synthesis and elucidating the molecular mechanisms that regulate inositol synthesis will contribute fundamental insight into cellular processes that are mediated by inositol compounds and will provide a foundation to understand numerous disease processes that result from perturbation of inositol homeostasis. In addition, elucidating the mechanisms of action of inositol-depleting drugs may suggest new strategies for the design of second-generation pharmaceuticals to treat psychiatric disorders and other illnesses.

摘要

肌醇是所有肌醇化合物的前体,对真核细胞的生存能力至关重要。众多细胞过程和信号功能都依赖于肌醇化合物,其合成受到干扰会导致多种人类疾病。尽管已经开展了大量研究来了解肌醇化合物的功能,尤其是磷脂酰肌醇和肌醇磷酸,但对控制肌醇生物合成的调节和稳态机制的关注在很大程度上被忽视了。因此,人们对人体细胞中肌醇合成的调控方式知之甚少。确定肌醇合成的生理调节因子并阐明调节肌醇合成的分子机制,将有助于深入了解由肌醇化合物介导的细胞过程,并为理解因肌醇稳态失衡导致的众多疾病过程提供基础。此外,阐明肌醇消耗药物的作用机制可能会为设计治疗精神疾病和其他疾病的第二代药物提供新策略。

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