Neuroprotective properties of mildronate, a small molecule, in a rat model of Parkinson's disease.
Neuroprotective properties of mildronate, a small molecule, in a rat model of Parkinson's disease.
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DOI：
10.3390/ijms11114465
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发表时间：
2010-11-09
影响因子：
5.6
通讯作者：
Vinters HV
中科院分区：
文献类型：
--
作者：
Klusa VZ;Isajevs S;Svirina D;Pupure J;Beitnere U;Rumaks J;Svirskis S;Jansone B;Dzirkale Z;Muceniece R;Kalvinsh I;Vinters HV
先前，我们发现米膦酸盐[3-（2,2,2-三甲基肼）丙酸二水合物]是一种带电荷的氮和氧原子的小分子，可以保护被复合物I抑制剂改变的线粒体代谢，并在叠氮胸腺嘧啶-神经毒性小鼠模型中具有神经保护作用。在本研究中，我们研究了米屈酸钠对帕金森病（PD）大鼠模型的影响，该模型是通过单侧纹状体内注射神经毒素6-羟多巴胺（6-OHDA）产生的。我们评估了参与信号级联反应并提供神经和胶质整合的细胞生物标志物的表达：神经元标志物TH（酪氨酸羟化酶）；泛素（一种参与泛素-蛋白酶体降解系统的调节肽）；Notch-3（祖细胞标记）；IBA-1（小胶质细胞的标记物）；胶质原纤维酸性蛋白（GFAP）；诱导型一氧化氮合酶，iNOS（炎症标志物）。数据显示，在6- ohda损伤的纹状体中，米屈膦酸钠完全阻止了TH的丢失，刺激了Notch-3的表达，降低了泛素、GFAP和iNOS的表达。这些结果为米屈酸钠控制一系列细胞蛋白表达的能力提供了证据，从而在大鼠帕金森病模型的神经元和神经胶质细胞中赋予多方面的稳态机制。我们认为，在帕金森病的早期阶段，使用米膦酸盐可以延缓或阻止这种神经退行性疾病的进展。
Previously, we have found that mildronate [3-(2,2,2-trimethylhydrazinium) propionate dihydrate], a small molecule with charged nitrogen and oxygen atoms, protects mitochondrial metabolism that is altered by inhibitors of complex I and has neuroprotective effects in an azidothymidine-neurotoxicity mouse model. In the present study, we investigated the effects of mildronate in a rat model of Parkinson’s disease (PD) that was generated via a unilateral intrastriatal injection of the neurotoxin 6-hydroxydopamine (6-OHDA). We assessed the expression of cell biomarkers that are involved in signaling cascades and provide neural and glial integration: the neuronal marker TH (tyrosine hydroxylase); ubiquitin (a regulatory peptide involved in the ubiquitin-proteasome degradation system); Notch-3 (a marker of progenitor cells); IBA-1 (a marker of microglial cells); glial fibrillary acidic protein, GFAP (a marker of astrocytes); and inducible nitric oxide synthase, iNOS (a marker of inflammation). The data show that in the 6-OHDA-lesioned striatum, mildronate completely prevented the loss of TH, stimulated Notch-3 expression and decreased the expression of ubiquitin, GFAP and iNOS. These results provide evidence for the ability of mildronate to control the expression of an array of cellular proteins and, thus, impart multi-faceted homeostatic mechanisms in neurons and glial cells in a rat model of PD. We suggest that the use of mildronate provides a protective effect during the early stages of PD that can delay or halt the progression of this neurodegenerative disease.
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影响因子：
15.9
作者：
Hernández, F;Díaz-Hernández, M;Lucas, JJ
通讯作者：
Lucas, JJ
影响因子：
3.6
作者：
Diamant, S;Rosenthal, D;Goloubinoff, P
通讯作者：
Goloubinoff, P
影响因子：
3.4
作者：
Depino, AM;Earl, C;Oertel, WH
通讯作者：
Oertel, WH
帕金森氏病，暴露于传染性剂和农药以及脑损伤的发生：神经炎症的作用。
影响因子：
10.4
作者：
Liu B;Gao HM;Hong JS
通讯作者：
Hong JS
影响因子：
25
作者：
Höglinger, GU;Rizk, P;Hirsch, EC
通讯作者：
Hirsch, EC