Environmental pollutant, Lead (Pb) is known to induce neurotoxicity in human. The central nervous system is the most vulnerable to the minute levels of Pb induced toxicity. Pb has been linked to Alzheimer's disease (AD) as a probable risk factor, as it shows epigenetic and developmental link associated with Alzheimer's disease-like pathology. Beta amyloid peptides were considered as the crucial factors in the beta amyloid plaque formation in Alzheimer's disease brain. In this context, we investigated the molecular mechanism involved in the development of Pb induced Alzheimer's disease in in vitro. Previous data from our studies have reported that Pb in the presence of beta Amyloid peptide (1-40) and (25-35) induces more apoptosis than individual exposures. Here, to further evaluate the molecular mechanism underlying Pb induced Alzheimer's disease; we focussed on the involvement of calcium signalling in inducing cell death. Our experimental observations suggesting that Pb in the presence of beta amyloid peptide alters intracellular calcium levels, which leads to the increased beta-secretase activity, which further promotes the generation of beta amyloid peptides. It also showed depression in the levels of GAP-43 expression, inhibition of PKC activity and altering synaptic activity further leads to cell death.

中文翻译：

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由于Pb和淀粉样蛋白肽引起的细胞钙耗竭，导致GAP-43失活：一种体外方法。

已知环境污染物铅（Pb）会诱发人体神经毒性。中枢神经系统最容易受到铅引起的微量毒性的伤害。铅与阿尔茨海默氏病（AD）可能是危险因素，因为它显示出与阿尔茨海默氏病样病理相关的表观遗传和发育联系。β淀粉样蛋白肽被认为是阿尔茨海默氏病脑中β淀粉样蛋白斑块形成的关键因素。在这种情况下，我们调查了体外铅引起的铅诱导的阿尔茨海默氏病发展的分子机制。我们研究的先前数据已报道，在存在β淀粉样肽（1-40）和（25-35）的情况下，铅比单独暴露诱导的细胞凋亡更多。这里，进一步评估铅引起的阿尔茨海默氏病的分子机制；我们专注于钙信号传导在诱导细胞死亡中的参与。我们的实验观察结果表明，存在β淀粉样蛋白肽的Pb会改变细胞内钙水平，从而导致增加β分泌酶的活性，从而进一步促进β淀粉样蛋白肽的产生。它还显示GAP-43表达水平下降，PKC活性抑制和突触活性改变进一步导致细胞死亡。这进一步促进了β淀粉样蛋白肽的产生。它还显示GAP-43表达水平下降，PKC活性抑制和突触活性改变进一步导致细胞死亡。这进一步促进了β淀粉样蛋白肽的产生。它还显示GAP-43表达水平下降，PKC活性抑制和突触活性改变进一步导致细胞死亡。