Department of Neurochemistry, NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA.
Mol Cell Endocrinol. 2011 Aug 22;343(1-2):1-6. doi: 10.1016/j.mce.2011.06.011. Epub 2011 Jun 25.
Hydroxysteroid (17β) dehydrogenase 10 (HSD10), the HSD17B10 gene product, is a mitochondrial NAD(+)-dependent dehydrogenase. There are two outstanding features of this vital enzyme: (a) the versatility of its catalytic endowment is attributed to the flexibility of its active site to accommodate diverse substrates such as steroids, fatty acids, bile acid, and xenobiotics; (b) its capacity to bind other proteins and peptides. For example, it tightly binds with three identical subunits to compose a homotetramer. The homotetramer then binds with two other proteins, namely, RNA (guanine-9-)methyl-transferase domain containing-1 and KIAA0391, to form mitochondrial RNase P. Furthermore, various HSD10 functions are inhibited when the enzyme is bound by amyloid-β peptide or estrogen receptor alpha. Missense mutations of HSD10 may cause neurodegeneration related to HSD10 deficiency, whereas a silent mutation of HSD10 results in mental retardation, choreoathetosis and abnormal behavior (MRXS10). The clinical condition of some HSD10 patients mimics mitochondrial disorders. Since normal HSD10 function is essential for brain cognitive activity, elevated levels of HSD10 found in brains of Alzheimer disease (AD) patients and mouse AD model might counterbalance the inhibition of HSD10 by amyloid-β peptide. The investigation of HSD10 may lead to a better understanding of AD pathogenesis.
羟甾体 17β 脱氢酶 10（HSD10）是 HSD17B10 基因的产物，是一种线粒体 NAD（+）依赖性脱氢酶。这种重要的酶有两个显著特点：（a）其催化赋存的多功能性归因于其活性部位的灵活性，使其能够适应各种底物，如类固醇、脂肪酸、胆汁酸和外源性物质；（b）其与其他蛋白质和肽结合的能力。例如，它与三个相同的亚基紧密结合，组成同源四聚体。然后，同源四聚体与另外两种蛋白质，即 RNA（鸟嘌呤-9-）甲基转移酶结构域包含 1 和 KIAA0391 结合，形成线粒体核糖核酸酶 P。此外，当酶与淀粉样β肽或雌激素受体α结合时，各种 HSD10 功能受到抑制。HSD10 的错义突变可能导致与 HSD10 缺乏相关的神经退行性变，而 HSD10 的无义突变则导致智力迟钝、舞蹈手足徐动症和异常行为（MRXS10）。一些 HSD10 患者的临床表现类似于线粒体疾病。由于正常 HSD10 功能对大脑认知活动至关重要，因此在阿尔茨海默病（AD）患者和 AD 模型小鼠的大脑中发现的 HSD10 水平升高可能会抵消淀粉样β肽对 HSD10 的抑制作用。对 HSD10 的研究可能有助于更好地理解 AD 的发病机制。
