| 1 | Curr. Drug Metab. 2007 Apr 8: 245-66 |
|---|---|
| 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。 |
| 抽象的 | 细胞在母胎界面表达挪作他用leamine 2,3 dioxygenase (IDO) to consume all local tryptophan for the express purpose of starving adjacent maternal T cells of this most limiting and essential amino acid. This stops local T cell proliferation to ultimately result in the most dramatic example of immune tolerance, acceptance of the fetus. By contrast, inhibition of IDO using 1-methyl-tryptophan causes a sudden catastrophic rejection of the mammalian fetus. Immunomodulatory factors including IFNgamma, TNFalpha, IL-1, and LPS use IDO induction in responsive antigen presenting cells (APCs) also to transmit tolerogenic signals to T cells. Thus it makes sense to consider IDO induction towards tolerance for autoimmune diseases in general. Approaches to cell specific therapeutic IDO induction with NAD precursor supplementation to prevent the collateral non-T cell pathogenesis due to chronic TNFalpha-IDO activated tryptophan depletion in autoimmune diseases are reviewed. Tryptophan is an essential amino acid most immediately because it is the only precursor for the endogenous biosynthesis of nicotinamide adenine dinucleotide (NAD). Both autoimmune disease and the NAD deficiency disease pellagra occur in women at greater than twice the frequency of occurrence in men. The importance of IDO dysregulation manifest as autoimmune pellagric dementia is genetically illustrated for Nasu-Hakola Disease (or PLOSL), which is caused by a mutation in the IDO antagonizing genes TYROBP/DAP12 or TREM2. Loss of function leads to psychotic symptoms rapidly progressing to presenile dementia likely due to unchecked increases in microglial IDO expression, which depletes neurons of tryptophan causing neurodegeneration. 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). Next,PGD(2) is converted to the anti-inflammatory prostaglandin, 15d-PGJ(2). These prostaglandins exert potent anti-inflammatory activities through endogenous signaling mechanisms involving the GPCRs EP2, EP4, and DP1 along with PPARgamma respectively. Nicotinamide prevents type 1 diabetes and ameliorates multiple sclerosis in animal models, while nothing is known about the therapeutic potential of nicotinamide riboside. Alternatively the direct targeting of the non-redox NAD-dependent proteins using resveratrol to activate SIRT1 or PJ34 in order to inhibit PARP1 and prevent autoimmune pathogenesis are also given consideration. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 2 | J Clin Psychopharmacol 2008 Jun 28: 264-370 |
| PMID | 18480682 |
| 标题 | A randomized, crossover comparison of herbal medicine and bromocriptine against risperidone-induced hyperprolactinemia in patients with schizophrenia. |
| 抽象的 | Hyperprolactinemia is a common adverse effect that occurs as a result of antipsychotic therapies, which often results in discontinuation. Empirical evidence has shown that some herbal medicines have suppressive effects on prolactin (PRL) hyperactivities. This study was designed to compare the herbal preparation called Peony-Glycyrrhiza Decoction (PGD）与溴封然（BMT），一种多巴胺激动剂广泛用于pRL分泌疾病，用于治疗利培酮诱导的高乳乳酸化血症血症。二十schizophrenicwomen who were under risperidone maintenance treatment, diagnosed with hyperprolactinemia (serum PRL levels >50 mug/L), and currently experiencing oligomenorrhea or amenorrhea were selected for the study. Subjects were randomized to additional treatment withPGD(45 g/d) followed by BMT (5 mg/d) or BMT followed byPGD在同一剂量为4周,智慧h an interval of 4-week washout period between 2 treatment sessions. The severity of psychotic symptoms, adverse events, serum PRL, estradiol, testosterone, and progesterone levels were examined at baseline and end point. Peony-Glycyrrhiza Decoction treatment produced a significant baseline-end point decrease in serum PRL levels, without exacerbating psychosis and changing other hormones, and the decreased amplitudes were similar to those of BMT (24% vs 21%-38%). Moreover, there was a significantly greater proportion of patients duringPGDtreatment than BMT treatment showing improvements on adverse effects associated with hyperprolactinemia (56% vs 17%, P = 0.037). These results suggest that the herbal therapy can yield additional benefits while having comparable efficacy in treating antipsychotic-induced hyperprolactinemia in individuals withschizophrenia. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 3 | J Clin Psychopharmacol 2008 Jun 28: 264-370 |
| PMID | 18480682 |
| 标题 | A randomized, crossover comparison of herbal medicine and bromocriptine against risperidone-induced hyperprolactinemia in patients with schizophrenia. |
| 抽象的 | Hyperprolactinemia is a common adverse effect that occurs as a result of antipsychotic therapies, which often results in discontinuation. Empirical evidence has shown that some herbal medicines have suppressive effects on prolactin (PRL) hyperactivities. This study was designed to compare the herbal preparation called Peony-Glycyrrhiza Decoction (PGD）与溴封然（BMT），一种多巴胺激动剂广泛用于pRL分泌疾病，用于治疗利培酮诱导的高乳乳酸化血症血症。二十schizophrenicwomen who were under risperidone maintenance treatment, diagnosed with hyperprolactinemia (serum PRL levels >50 mug/L), and currently experiencing oligomenorrhea or amenorrhea were selected for the study. Subjects were randomized to additional treatment withPGD(45 g/d) followed by BMT (5 mg/d) or BMT followed byPGD在同一剂量为4周,智慧h an interval of 4-week washout period between 2 treatment sessions. The severity of psychotic symptoms, adverse events, serum PRL, estradiol, testosterone, and progesterone levels were examined at baseline and end point. Peony-Glycyrrhiza Decoction treatment produced a significant baseline-end point decrease in serum PRL levels, without exacerbating psychosis and changing other hormones, and the decreased amplitudes were similar to those of BMT (24% vs 21%-38%). Moreover, there was a significantly greater proportion of patients duringPGDtreatment than BMT treatment showing improvements on adverse effects associated with hyperprolactinemia (56% vs 17%, P = 0.037). These results suggest that the herbal therapy can yield additional benefits while having comparable efficacy in treating antipsychotic-induced hyperprolactinemia in individuals withschizophrenia. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 4 | Schizophr. Res. 2010 Dec 124: 183-91 |
| PMID | 20675101 |
| 标题 | MicroRNA expression profiling in the prefrontal cortex of individuals affected with schizophrenia and bipolar disorders. |
| 抽象的 | MicroRNAs (miRNAs) are a large family of small non-coding RNAs which negatively control gene expression at both the mRNA and protein levels. The number of miRNAs identified is growing rapidly and approximately one-third is expressed in the brain where they have been shown to affect neuronal differentiation, synaptosomal complex localization and synapse plasticity, all functions thought to be disrupted inschizophrenia. Here we investigated the expression of 667 miRNAs (miRBase v.13) in the prefrontal cortex of individuals withschizophrenia(SZ, N = 35) and bipolar disorder (BP, N = 35) using a real-time PCR-based Taqman Low Density Array (TLDA). After extensive QC steps, 441 miRNAs were included in the final analyses. At a FDR of 10%, 22 miRNAs were identified as being differentially expressed between cases and controls, 7 dysregulated in SZ and 15 in BP. Using in silico target gene prediction programs, the 22miRNAs were found to target brain specific genes contained within networks overrepresented for neurodevelopment, behavior, and SZ and BP disease development. In an initial attempt to corroborate some of these predictions, we investigated the extent of correlation between the expressions of hsa-mir-34a, -132 and -212 and their predicted gene targets. mRNA expression of tyrosine hydroxylase (TH), phosphogluconate dehydrogenase (PGD) and metabotropic glutamate receptor 3 (GRM3) was measured in the SMRI sample. Hsa-miR-132 and -212 were negatively correlated with TH (p = 0.0001 and 0.0017) and withPGD（分别为p = 0.0054和0.017）。 |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 5 | Neurosci. Lett. 2015 Oct 606: 60-5 |
| PMID | 26297122 |
| 标题 | Studies on the regulatory effect of Peony-Glycyrrhiza Decoction on prolactin hyperactivity and underlying mechanism in hyperprolactinemia rat model. |
| 抽象的 | Clinical trials have demonstrated the beneficial effects of Peony-Glycyrrhiza Decoction (PGD）减轻抗精神病药诱导的高泌乳素血症（HyperPRL）schizophrenic患者。在以前的实验中PGD在MMQ细胞中抑制催乳素（PRL）水平，涉及调节D2受体（DRD2）和多巴胺转运蛋白（DAT）的表达。在本研究中，使用多巴胺阻滞剂甲状腺素（MCP）诱导的HyperPRL女性大鼠模型进一步确认PGDand underlying mechanism. In MCP-induced hyperPRL rats, the elevated serum PRL level was significantly suppressed by eitherPGD（2.5-10 g/kg）或溴封然（BMT）（0.6 mg/kg）给药14天。但是，在MCP引起的大鼠中，仅PGDrestored the under-expressed serum progesterone (P) to control level. BothPGDand BMT administration restore the under-expression of DRD2, DAT and TH resulted from MCP in pituitary gland and hypothalamus. Compared to untreated group, hyperPRL animals had a marked reduction on DRD2 and DAT expression in the arcuate nucleus.PGD(10 g/kg) and BMT (0.6 mg/kg) treatment significant reversed the expression of DRD2 and DAT. Collectively, the anti-hyperPRL activity ofPGDassociates with the modulation of dopaminergic neuronal system and the restoration of serum progesterone level. Our finding supportsPGD作为针对HyperPRL的有效代理。 |
| SCZ关键字 | 精神分裂症，精神分裂症 |