Laboratory of Neurotoxins, Brain Institute of Rio Grande do Sul (BRAINS) and Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre CEP 90610-000, RS, Brazil.
Center of Biotechnology, Graduate Program in Cellular and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre CEP 91501-970, RS, Brazil.
Int J Mol Sci. 2022 Mar 13;23(6):3091. doi: 10.3390/ijms23063091.
Alzheimer's disease (AD) causes dementia and memory loss in the elderly. Deposits of beta-amyloid peptide and hyperphosphorylated tau protein are present in a brain with AD. A filtrate of culture was previously found to induce hyperphosphorylation of tau in vivo, suggesting that bacterial exotoxins could permeate the blood-brain barrier and directly induce tau's phosphorylation. , which infects ~60% of the world population and causes gastritis and gastric cancer, produces a pro-inflammatory urease (HPU). Here, the neurotoxic potential of HPU was investigated in cultured cells and in rats. SH-SY5Y neuroblastoma cells exposed to HPU (50-300 nM) produced reactive oxygen species (ROS) and had an increased [Ca]i. HPU-treated BV-2 microglial cells produced ROS, cytokines IL-1β and TNF-α, and showed reduced viability. Rats received daily i.p., HPU (5 µg) for 7 days. Hyperphosphorylation of tau at Ser199, Thr205 and Ser396 sites, with no alterations in total tau or GSK-3β levels, and overexpression of Iba1, a marker of microglial activation, were seen in hippocampal homogenates. HPU was not detected in the brain homogenates. Behavioral tests were performed to assess cognitive impairments. Our findings support previous data suggesting an association between infection by and tauopathies such as AD, possibly mediated by its urease.
阿尔茨海默病（AD）会导致老年人痴呆和记忆力减退。AD 患者的大脑中存在β-淀粉样肽和过度磷酸化的 tau 蛋白沉积。先前发现，培养物的滤液可在体内诱导 tau 的过度磷酸化，这表明细菌外毒素可能穿透血脑屏障并直接诱导 tau 的磷酸化。幽门螺杆菌（）感染了世界上约 60%的人口，可引起胃炎和胃癌，并产生一种促炎的脲酶（HPU）。在这里，研究了 HPU 在培养细胞和大鼠中的神经毒性潜力。暴露于 HPU（50-300 nM）的 SH-SY5Y 神经母细胞瘤细胞会产生活性氧（ROS）并增加 [Ca]i。经 HPU 处理的 BV-2 小胶质细胞会产生 ROS、细胞因子 IL-1β 和 TNF-α，并表现出活力降低。大鼠每天接受腹腔内注射 HPU（5 µg），共 7 天。在海马匀浆中，tau 在 Ser199、Thr205 和 Ser396 位点的过度磷酸化，总 tau 或 GSK-3β 水平没有改变，Iba1 过度表达，Iba1 是小胶质细胞激活的标志物。在脑匀浆中未检测到 HPU。进行了行为测试以评估认知障碍。我们的发现支持了先前的数据，表明 感染与 AD 等 tau 病之间存在关联，可能与其脲酶有关。
