The anticholinesterase phenserine and its enantiomer posiphen as 5'untranslated-region-directed translation blockers of the Parkinson's alpha synuclein expression.
The anticholinesterase phenserine and its enantiomer posiphen as 5'untranslated-region-directed translation blockers of the Parkinson's alpha synuclein expression.
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DOI：
10.1155/2012/142372
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Rogers JT
中科院分区：
文献类型：
--
作者：
Mikkilineni S;Cantuti-Castelvetri I;Cahill CM;Balliedier A;Greig NH;Rogers JT
限制帕金森病（PD）患者脑中α-突触核蛋白（α-syn）的表达得到了令人信服的支持。SNCA基因拷贝数的增加可遗传性地导致家族性PD，其中该致病蛋白的增加的剂量与症状的严重程度相关（SNCA基因的三倍化导致PD患者的痴呆）。基因启动子多态性增加α-突触核蛋白表达，是PD的风险。胆碱酯酶抑制剂可以在临床上减缓PD病因学后期的认知下降，类似于其在阿尔茨海默病（AD）中的广泛使用。与此相关的是，我们确定了耐受性良好的抗胆碱酯酶剂phenserine阻断了神经SNCA mRNA的翻译，并以类似于其限制AD特异性淀粉样前体蛋白（APP）表达的作用的方式通过其5′非翻译区（5′UTR）进行了靶向测试。Posiphen，其耐受性更好的（+）对映体（无抗胆碱酯酶作用），抑制神经α-突触核蛋白翻译。posiphen的初级代谢类似物，同样，使用从表达人SNCA基因的帕金森氏转基因小鼠的脑中离体生长的初级胎儿神经元进行表征。
There is compelling support for limiting expression of alpha-synuclein (α-syn) in the brains of Parkinson's disease (PD) patients. An increase of SNCA gene copy number can genetically cause familial PD where increased dose of this pathogenic protein correlates with severity of symptoms (triplication of the SNCA gene causes dementia in PD patients). Gene promoter polymorphisms were shown to increase α-synuclein expression as a risk for PD. Cholinesterase inhibitors can clinically slow cognitive decline in the later stages of PD etiology similar to their widespread use in Alzheimer's disease (AD). Pertinent to this, we identified that the well-tolerated anticholinesterase, phenserine, blocked neural SNCA mRNA translation and tested for targeting via its 5′untranslated region (5′UTR) in a manner similar to its action to limit the expression of the AD-specific amyloid precursor protein (APP). Posiphen, its better-tolerated (+) enantiomer (devoid of anticholinesterase action), repressed neural α-synuclein translation. Primary metabolic analogs of posiphen were, likewise, characterized using primary fetal neurons grown ex vivo from the brains of Parkinson's transgenic mice expressing the human SNCA gene.
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影响因子：
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DOI：
10.1097/01.jnen.0000190063.90440.69
发表时间：
2005-12-01
影响因子：
3.2
作者：
Cantuti-Castelvetri, I;Klucken, J;Standaert, DG
通讯作者：
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