| 1 | Curr。药物代谢。2007年4月8日：245-66 |
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| PMID | 17430113 |
| 标题 | IDO介导的耐受性治疗自身免疫性疾病的药理靶向。 |
| Abstract | 母体界面的细胞表达吲哚胺2,3二加氧酶（IDO）食用所有局部色氨酸，以明确目的是饿死这种最有限的和必需的氨基酸的相邻母体T细胞。这停止了局部T细胞增殖，最终导致免疫耐受性，接受胎儿的最戏剧性的例子。相比之下，使用1-甲基 - 色氨酸对IDO的抑制会导致哺乳动物胎儿突然灾难性排斥。免疫调节因素在内，包括IFNGAMMA，TNFALPHA，IL-1和LPS在响应式抗原呈递细胞（APC）中使用IDO诱导也将耐受性信号传递到T细胞。因此，考虑一般来说，考虑对自身免疫性疾病的耐受性，这是有意义的。综述了自身免疫性疾病中的慢性TNFalpha-IDO激活的色氨酸耗竭，以防止侧支非T细胞发病机理的NAD前体的特异性IDO诱导方法。色氨酸是最重要的氨基酸，因为它是烟酰胺腺苷二核苷酸（NAD）内源性生物合成的唯一前体。女性的自身免疫性疾病和NAD缺乏疾病都大于男性发生频率的两倍。IDO失调的重要性表现为自身免疫性沉淀痴呆症在NASU-Hakola疾病（或PLOSL）上是由IDO拮抗基因TyroBP/DAP12或Trem2引起的，这是NASU-Hakola病（或PLOSL）的遗传学。功能的丧失导致精神病症状迅速发展为老年痴呆，可能是由于小胶质细胞IDO表达不受检查的增加而导致的，这会消耗神经变性的神经元的神经元。 Administration of NAD precursors rescued entire mental hospitals of dementia patients literally overnight in the 1930's and NAD precursors should help Nasu-Hakola patients as well. NAD depletion mediated by peroxynitrate PARP1 activation is one of the few established mechanisms of necrosis. Chronic elevation of TNFalpha leading to necrotic events by NAD depletion in autoimmune disease likely occurs via combination of persistent IDO activation and iNOS-peroxynitrate activation of PARP1 both of which deplete NAD. Pharmacological doses of NAD precursors repeatedly provide dramatic therapeutic benefit for rheumatoid arthritis, type 1 diabetes, multiple sclerosis, colitis, other autoimmune diseases, andschizophrenia在诊所或动物模型中。总的来说，这些观察结果支持以下观点：自身免疫性疾病可能部分被视为局部表现出发炎靶组织的症状。因此，NAD前体的药理剂量（烟酸/烟酸，烟酰胺/烟酰胺或烟酰胺核糖苷）应被认为是对任何IDO诱导方案的治疗方案的治疗方案的潜在至关重要的，以治疗自身免疫性疾病。在NAD前体中不同，烟酸特异性激活了G蛋白偶联受体（GPCR）GPR109A，以产生诱导IDO的耐受性前列腺素PGE（2）和PGD（2）。接下来，PGD（2）转化为抗炎前列腺素，15d-PGJ（2）。这些前列腺素通过分别涉及GPCRS EP2，EP4和DP1的内源信号传导机制以及PPARGAMMA发挥有效的抗炎活性。烟酰胺可防止1型糖尿病并改善动物模型中的多发性硬化症，而对烟酰胺核糖苷的治疗潜力一无所知。或者，使用白藜芦醇激活非二氧化物NAD NAD依赖性蛋白的直接靶向SIRT1or PJ34 in order to inhibit PARP1 and prevent autoimmune pathogenesis are also given consideration. |
| SCZ关键字 | schizophrenia |
| 2 | Hum Psychopharmacol 2011 Oct 26: 445-50 |
| PMID | 21882241 |
| 标题 | 日本人群中SIRT1基因与甲基苯丙胺诱导的精神病之间没有显着关联。 |
| Abstract | We previously showed that the sirtuin 1 gene (SIRT1gene), one of the clock genes, was associated withschizophreniain a Japanese patient population. Because the symptoms of methamphetamine (METH)-induced psychosis are similar to those of paranoid typeschizophreniaand because not every METH user develops psychosis, it is conceivable that METH-induced psychosis andschizophreniahave common susceptibility genes. Therefore, we conducted an analysis of the association ofSIRT1gene with METH-induced psychosis, hypothesizing a significant relationship. This paper presents a case-control study of theSIRT1基因与冰毒在515年日本人(197年duced psychosis and 318 age-matched and sex-matched controls) with four tagging single nucleotide polymorphisms (rs12778366, rs2273773, rs4746720, and rs10997875), selected a priori using the HapMap database. rs10997875 (located in the 3' flanking region) was associated with METH-induced psychosis (unadjusted p(genotype) ?=?0.0203). However, these results became non-significant after Bonferroni correction (corrected p(genotype) ?=?0.0812). In the all-marker haplotype analysis, theSIRT1gene was not associated with METH-induced psychosis (p?=?0.146). 我们的发现表明SIRT1基因对日本人群中甲基苯丙胺诱导的精神病的发展没有贡献。但是，应进行使用较大样品的复制研究以获得结论性结果。 |
| SCZ关键字 | schizophrenia |
| 3 | 基因脑行为。2011年4月10日：257-63 |
| PMID | 20977650 |
| 标题 | 日本人群中的SIRT1基因，精神分裂症和躁郁症：一项协会研究。 |
| Abstract | 几条证据表明，昼夜节律的改变可能与精神疾病的病理生理有关schizophreniaand bipolar disorder (BP). A recent study reported thatSIRT1是在昼夜节律系统中起重要作用的分子。因此，评估SIRT1gene,schizophreniaand BP, we conducted a case-control study of Japanese population samples (1158schizophreniapatients, 1008 BP patients and 2127 controls) with four tagging SNPs (rs12778366, rs2273773, rs4746720 and rs10997875) in theSIRT1基因。标记性迹象联想分析用于评估等位基因和与？（2）测试的基因型关联，并通过可能比率检验评估了单倍型关联分析。我们在RS4746720之间显示了SIRT1gene andschizophreniain the allele and the genotype analysis. However, the significance of these associations did not survive after Bonferroni's correction for multiple testing. On the other hand, theSIRT1gene was associated with Japaneseschizophreniain a haplotype-wise analysis (global P(all markers) = 4.89 � 10(-15)). Also, four tagging SNPs in theSIRT1gene were not associated with BP. In conclusion, theSIRT1gene may play an important role in the pathophysiology ofschizophrenia在日本人口中。 |
| SCZ关键字 | schizophrenia |
| 4 | Psychiatry Res 2015 Feb 225: 744-5 |
| PMID | 25554355 |
| 标题 | 中国人口中，无声信息调节剂1（SIRT1）基因多态性与精神分裂症之间的关联。 |
| Abstract | -1 |
| SCZ关键字 | schizophrenia |
| 5 | 营养2016年2月32日：174-8 |
| PMID | 26706021 |
| 标题 | 白藜芦醇的有益行动：如何以及为什么？ |
| Abstract | Flavonoid resveratrol modulates the transcription factor NF-?B; inhibits the cytochrome P450 isoenzyme CYP1 A1; suppresses the expression and activity of cyclooxygenase enzymes; and modulates Fas/Fas-ligand-mediated apoptosis, p53, mammalian target of rapamycin, and cyclins and various phosphodiesterases. This increases the cytosolic cAMP that activates Epac1/CaMKK?/AMPK/SIRT1/PGC-1? pathway, which in turn facilitates increased oxidation of fatty acids, mitochondrial biogenesis, mitochondrial respiration, and gluconeogenesis. Resveratrol triggers apoptosis of activated T cells and suppresses tumor necrosis factor-?, interluekin-17 (IL-17), and other proinflammatory molecules, and thus is of benefit in autoimmune diseases. In addition, resveratrol inhibits expression of hypoxia-inducible factor-1? and vascular endothelial growth factor, explaining its effective action against cancer. Brain-derived neurotrophic factor (BDNF) that is involved in the pathogenesis of obesity, type 2 diabetes mellitus, and metabolic syndrome is also altered in depression,schizophrenia, bipolar disorder, and autism. We noted that BDNF protects against cytotoxic actions of alloxan, streptozotocin, and benzo(a)pyrene. Resveratrol prevents bisphenol A-induced autism, type 2 diabetes mellitus, and metabolic syndrome, suggesting that it may augment BDNF synthesis and action. We also observed that BDNF levels are low in type 2 diabetes mellitus and that BDNF enhances production of antiinflammatory lipid, lipoxin A4, whose levels are low in diabetes mellitus. Thus, resveratrol may augment production of lipoxin A4. Resveratrol alters gut microbiota and influences stem cell proliferation and differentiation. These pleiotropic actions of resveratrol may explain the multitude of its actions and benefits. |
| SCZ关键字 | schizophrenia |
| 6 | Mol. Neurobiol. 2016 May 53: 2498-509 |
| PMID | 26055227 |
| 标题 | Paliperidone通过抑制Ca（2+）涌入和SIRT1/MIR-134信号途径的调节，可保护SH-SY5Y细胞免受MK-801诱导的神经元损伤。 |
| Abstract | schizophreniais a serious psychotic disease. Recently, increasing evidences support that neurodegeneration occurs in the brain ofschizophreniapatients with progressive morphological changes. Paliperidone, an atypical antipsychotic drug, could attenuate psychotic symptom and protect neurons from different stressors. However, the underlying mechanisms are largely unknown. In this study, we used SH-SY5Y cells to evaluate the neuroprotective capability of paliperidone against the neurotoxicity induced by N-methyl-D-aspartate receptor antagonist, MK-801. And, we also explored the possible molecular mechanism. Neurotoxicity of 100�?M MK-801, which reduced the cell viability, was diminished by 100�?M paliperidone using MTT and LDH assays (both p?SIRT1and decrease of miR-134 expression (both p?SIRT1抑制剂烟酰胺阻断MK-801损伤效应并抑制miR-134表达。综上所述，我们的结果表明，棕榈酮可以通过抑制Ca（2+）流入和调节来保护SH-SY5Y细胞免受MK-801的诱导神经毒性。SIRT1/miR-134途径，为schizophrenia. |
| SCZ关键字 | schizophrenia |