The inositol pyrophosphate pathway in health and diseases.
The inositol pyrophosphate pathway in health and diseases.
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DOI：
10.1111/brv.12392
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发表时间：
2018-05
影响因子：
--
通讯作者：
Chakraborty A
中科院分区：
文献类型：
--
作者：
Chakraborty A
肌醇焦磷酸 (IPP) 存在于植物、粘菌、真菌和哺乳动物等生物体中。不同类别的激酶从磷酸肌醇 (IP) 中产生不同形式的含能量二磷酸盐 IPP。相反，多磷酸磷酸水解酶使IPP去磷酸化以再生相应的IP。 IPP 和/或其代谢酶通过不同的机制调节许多蛋白质，从而调节各种细胞生物过程。在过去的十年中，人们在哺乳动物系统中进行了广泛的研究，特别是在相关酶的敲除小鼠模型中。这些研究的结果表明，IPP 途径对器官发育有影响，尤其是大脑和睾丸。相反，删除该通路中的特定酶可以保护小鼠免受多种疾病的影响，例如饮食诱导的肥胖（DIO）、2型糖尿病（T2D）、脂肪肝、细菌感染、血栓栓塞、癌症转移和衰老。此外，在小鼠中对同类酶的药理学抑制验证了该途径在心脏代谢疾病中的治疗重要性。这篇综述批判性地分析了这些发现，并总结了 IPP 途径在哺乳动物健康和疾病中的重要性。它还评估了在疾病治疗中针对该途径的益处和风险。最后，讨论了哺乳动物IPP研究的未来方向。
Inositol pyrophosphates (IPPs) are present in organisms ranging from plants, slime moulds and fungi to mammals. Distinct classes of kinases generate different forms of energetic diphosphate-containing IPPs from inositol phosphates (IPs). Conversely, polyphosphate phosphohydrolase enzymes dephosphorylate IPPs to regenerate the respective IPs. IPPs and/or their metabolizing enzymes regulate various cell biological processes by modulating many proteins via diverse mechanisms. In the last decade, extensive research has been conducted in mammalian systems, particularly in knockout mouse models of relevant enzymes. Results obtained from these studies suggest impacts of the IPP pathway on organ development, especially of brain and testis. Conversely, deletion of specific enzymes in the pathway protects mice from various diseases such as diet-induced obesity (DIO), type-2 diabetes (T2D), fatty liver, bacterial infection, thromboembolism, cancer metastasis and aging. Furthermore, pharmacological inhibition of the same class of enzymes in mice validates the therapeutic importance of this pathway in cardio-metabolic diseases. This review critically analyses these findings and summarizes the significance of the IPP pathway in mammalian health and diseases. It also evaluates benefits and risks of targeting this pathway in disease therapies. Finally, future directions of mammalian IPP research are discussed.
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影响因子：
7.3
作者：
Chakraborty A;Kim S;Snyder SH
通讯作者：
Snyder SH
影响因子：
64.5
作者：
Chakraborty A;Koldobskiy MA;Bello NT;Maxwell M;Potter JJ;Juluri KR;Maag D;Kim S;Huang AS;Dailey MJ;Saleh M;Snowman AM;Moran TH;Mezey E;Snyder SH
通讯作者：
Snyder SH
影响因子：
4.8
作者：
Caffrey, JJ;Safrany, ST;Shears, SB
通讯作者：
Shears, SB
DOI：
10.1073/pnas.0909176106
发表时间：
2009-12-15
影响因子：
11.1
作者：
Azevedo, Cristina;Burton, Adam;Saiardi, Adolfo
通讯作者：
Saiardi, Adolfo
DOI：
10.1002/stem.2645
发表时间：
2017-08
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Boregowda SV;Ghoshal S;Booker CN;Krishnappa V;Chakraborty A;Phinney DG
通讯作者：
Phinney DG