The high-affinity D2/D3 agonist D512 protects PC12 cells from 6-OHDA-induced apoptotic cell death and rescues dopaminergic neurons in the MPTP mouse model of Parkinson's disease.
The high-affinity D2/D3 agonist D512 protects PC12 cells from 6-OHDA-induced apoptotic cell death and rescues dopaminergic neurons in the MPTP mouse model of Parkinson's disease.
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高亲和力 D2/D3 激动剂 D512 可保护 PC12 细胞免遭 6-OHDA 诱导的细胞凋亡，并拯救帕金森病 MPTP 小鼠模型中的多巴胺能神经元。
DOI：
10.1111/jnc.12767
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发表时间：
2014-10
影响因子：
4.7
通讯作者：
Dutta AK
中科院分区：
文献类型：
--
作者：
Shah M;Rajagopalan S;Xu L;Voshavar C;Shurubor Y;Beal F;Andersen JK;Dutta AK
本研究采用高亲和力多功能D2/D3受体激动剂D-512进行体内外实验，探讨其在帕金森病（PD）模型中的潜在神经保护作用及其潜在机制。D-512在体外预处理可使大鼠肾上腺嗜铬细胞瘤PC 12细胞免于6-羟基多巴胺（6-OHDA）诱导的毒性，并呈剂量依赖性。发现神经保护与细胞内活性氧、脂质过氧化和DNA损伤的减少一致。在体内，0.5 mg/kg D-512预处理可预防与1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）全身给药相关的神经退行性表型，包括纹状体多巴胺（DA）损失、黑质（SN）DA能神经元数量减少和运动功能障碍。这些观察结果强烈表明，多功能药物D-512可能构成一种新的可行的治疗PD。
In this study, in vitro and in vivo experiments were carried out with the high-affinity multifunctional D2/D3 agonist D-512 in order to explore its potential neuroprotective effects in models of Parkinson’s disease (PD) and the potential mechanism(s) underlying such properties. Pretreatment with D-512 in vitro was found to rescue rat adrenal phaeochromocytoma PC12 cells from toxicity induced by 6-hydroxydopamine (6-OHDA) administration in a dose-dependent manner. Neuroprotection was found to coincide with reductions in intracellular reactive oxygen species, lipid peroxidation, and DNA damage. In vivo, pretreatment with 0.5 mg/kg D-512 was protective against neurodegenerative phenotypes associated with systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), including losses in striatal dopamine (DA), reductions in numbers of DAergic neurons in the substantia nigra (SN), and locomotor dysfunction. These observations strongly suggest that the multifunctional drug D-512 may constitute a novel viable therapy for PD.
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影响因子：
168.9
作者：
Chartier-Harlin, MC;Kachergus, J;Destée, A
通讯作者：
Destée, A
影响因子：
14.8
作者：
Jackson-Lewis, Vernice;Przedborski, Serge
通讯作者：
Przedborski, Serge
影响因子：
4.8
作者：
Lee, Donna W.;Rajagopalan, Subramanian;Andersen, Julie K.
通讯作者：
Andersen, Julie K.
影响因子：
4.7
作者：
BEAL, MF;MATSON, WR;BIRD, ED
通讯作者：
BIRD, ED
DOI：
10.1016/0278-5846(89)90121-8
发表时间：
1989-01-01
影响因子：
5.6
作者：
HORNYKIEWICZ, O
通讯作者：
HORNYKIEWICZ, O