Determinants of denervation-independent depletion of putamen dopamine in Parkinson's disease and multiple system atrophy.
Determinants of denervation-independent depletion of putamen dopamine in Parkinson's disease and multiple system atrophy.
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DOI：
10.1016/j.parkreldis.2016.12.011
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发表时间：
2017-03
影响因子：
4.1
通讯作者：
Sharabi Y
中科院分区：
文献类型：
--
作者：
Goldstein DS;Sullivan P;Holmes C;Mash DC;Kopin IJ;Sharabi Y
严重的壳核多巴胺耗竭是帕金森病（PD）和多系统萎缩（MSA）的特征。这种消耗的程度比单独用黑质纹状体多巴胺能末梢的损失所能解释的还要大。我们使用壳核组织水平和半胱氨酰和母体儿茶酚的比率来探索PD和MSA中可能的去神经依赖性多巴胺合成和命运异常。5-S-半胱氨酰多巴本文测定了17例PD、25例MSA患者和30例正常对照的死后壳核组织中内源性儿茶酚（DA）及其胞浆代谢产物的含量（Cys-DA、3，4-二羟基苯乙酸、3，4-二羟基苯基乙醇和3，4-二羟基苯乙醛）和DA近端的酪氨酸羟基化产物（DOPA和Cys-DOPA）。PD和MSA组在母体或半胱氨酰儿茶酚的平均值方面没有差异，并且两组的数据被集中。在患者中，DA囊泡储存指数（DA与其细胞质代谢产物总和的比率）平均为对照组的54%（p = 0.001），L-芳香族氨基酸脱羧酶（LAAAD）活性指数（DA与其细胞质代谢产物总和与多巴+半胱氨酸多巴总和的比率）平均为对照组的21%（p < 0.0001）。神经支配指数（DOPA + Cys-DOPA的总和）平均为对照的63%（p = 0.01）。基于壳核中母体和半胱氨酰儿茶酚的模式，PD和MSA涉及囊泡摄取减少和残留多巴胺能末梢中LAAAD活性降低。这种结合似乎对这些疾病中的多巴胺耗竭有重要贡献。
Severe putamen dopamine depletion characterizes Parkinson’s disease (PD) and multiple system atrophy (MSA). The extent of the depletion is greater than can be accounted for by loss of nigrostriatal dopaminergic terminals alone. We used putamen tissue levels and ratios of cysteinyl and parent catechols to explore possible denervation-independent abnormalities of dopamine synthesis and fate in PD and MSA. 5-S-Cysteinyldopa (Cys-DOPA) is produced from spontaneous oxidation of DOPA and 5-S-cysteinyldopamine (Cys-DA) from spontaneous oxidation of DA. Post-mortem putamen tissue samples from 17 PD and 25 MSA patients and 30 controls were assayed for endogenous catechols including DA, its cytoplasmic metabolites (Cys-DA, 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxyphenylethanol, and 3,4-dihydroxyphenylacetaldehyde), and tyrosine hydroxylation products proximal to DA (DOPA and Cys-DOPA). The PD and MSA groups did not differ in mean values of parent or cysteinyl catechols, and the data for the two groups were lumped. In the patients an index of vesicular storage of DA (the ratio of DA to the sum of its cytoplasmic metabolites) averaged 54% of control (p = 0.001), and an index of L-aromatic-amino-acid decarboxylase (LAAAD) activity (the ratio of DA and the sum of its cytoplasmic metabolites to the sum of DOPA + Cys-DOPA) averaged 21% of control (p < 0.0001). An index of innervation (the sum of DOPA + Cys-DOPA) averaged 63% of control (p = 0.01). Based on patterns of parent and cysteinyl catechols in putamen, PD and MSA involve decreased vesicular uptake and decreased LAAAD activity in the residual dopaminergic terminals. The combination seems to contribute importantly to dopamine depletion in these diseases.
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影响因子：
11.2
作者：
HALLIDAY, GM;LI, YW;GEFFEN, LB
通讯作者：
GEFFEN, LB
影响因子：
4.1
作者：
Goldstein DS;Sullivan P;Holmes C;Kopin IJ;Sharabi Y;Mash DC
通讯作者：
Mash DC
帕金森病中有毒多巴胺代谢物 DOPAL 积累的决定因素。
影响因子：
4.7
作者：
Goldstein DS;Sullivan P;Holmes C;Miller GW;Alter S;Strong R;Mash DC;Kopin IJ;Sharabi Y
通讯作者：
Sharabi Y
DOI：
10.1124/jpet.115.230201
发表时间：
2016-02-01
影响因子：
3.5
作者：
Goldstein, David S.;Jinsmaa, Yunden;Sharabi, Yehonatan
通讯作者：
Sharabi, Yehonatan
影响因子：
--
作者：
DelleDonne, Anthony;Klos, Kevin J.;Dickson, Dennis W.
通讯作者：
Dickson, Dennis W.