Zinc Transporter mRNA Levels in Alzheimer's Disease Postmortem Brain
Zinc Transporter mRNA Levels in Alzheimer's Disease Postmortem Brain
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DOI：
10.3233/jad-2012-112105
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发表时间：
2012-01-01
影响因子：
4
通讯作者：
Johnston, Janet A.
中科院分区：
文献类型：
--
作者：
Beyer, Nancy;Coulson, David T. R.;Johnston, Janet A.
锌（Zn 2+）集中在突触前囊泡中，并在某些突触处与神经递质共同释放。Zn 2+可加速淀粉样β肽（A β）和tau蛋白的组装，所述tau蛋白是阿尔茨海默病（AD）中发现的神经病理学改变的中心。已报道AD死后脑组织中膜Zn 2+转运蛋白ZnT1、ZnT4和ZnT6的蛋白水平改变。本研究采用实时荧光定量PCR分析了5种已建立的（LIV1，ZIP1，ZnT1，ZnT4和ZnT6）和一种潜在的（PRNP）Zn2+转运蛋白在人死后脑组织中的mRNA水平。检查了四个皮质区域（颞中回、上级枕回、上级顶回和上级额回）和小脑。PRNP mRNA水平下降了30%左右，在所有四个皮质区域检查AD患者，但在小脑不变。与此相反，一些增加的mRNA水平的其他更确定的锌离子转运蛋白（LIV1，ZIP1，ZnT1，ZnT6）被发现在AD皮层。LIV 1、ZIP 1、ZnT1、ZnT4和ZnT6的mRNA水平与神经元特异性烯醇化酶mRNA水平的比值随病程进展和Braak分期的增加而显著增加。显着的相关性也确定了几个锌离子转运蛋白的mRNA水平之间的研究。这些表达变化可能反映或导致AD中改变的皮质Zn 2+分布，潜在地增加Zn 2+与A β或tau蛋白之间相互作用的可能性。
Zinc (Zn2+) is concentrated into pre-synaptic vesicles and co-released with neurotransmitter at some synapses. Zn2+ can accelerate assembly of the amyloid-beta peptides (A beta) and tau protein central to the neuropathological changes found in Alzheimer's disease (AD). Altered protein levels of the membrane Zn2+ transporters ZnT1, ZnT4, and ZnT6 have been reported in AD postmortem brain tissue. The present study analyzed mRNA levels of five established (LIV1, ZIP1, ZnT1, ZnT4, and ZnT6) and one potential (PRNP) Zn2+ transporter in human postmortem brain tissue from Braak-staged individuals with AD and controls using quantitative real-time PCR. Four cortical regions (middle temporal gyrus, superior occipital gyrus, superior parietal gyrus, and superior frontal gyrus) and cerebellum were examined. PRNP mRNA levels were decreased by similar to 30% in all four cortical regions examined in AD patients, but unchanged in the cerebellum. In contrast, some increases in mRNA levels of the other more established Zn2+ transporters (LIV1, ZIP1, ZnT1, ZnT6) were found in AD cortex. The ratios of the mRNA levels of LIV1, ZIP1, ZnT1, ZnT4, and ZnT6/mRNA level of neuron specific enolase increased significantly as the disease progressed and Braak stage increased. Significant correlations were also identified between mRNA levels of several of the Zn2+ transporters investigated. These expression changes could either reflect or cause the altered cortical Zn2+ distribution in AD, potentially increasing the likelihood of interactions between Zn2+ and A beta or tau protein.