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Heparan Sulfate Proteoglycans Undergo Differential Expression Alterations in Alzheimer Disease Brains
Journal of Neuropathology and Experimental Neurology ( IF 3.2 ) Pub Date : 2020-02-24 , DOI: 10.1093/jnen/nlaa016
Laura Lorente-Gea 1 , Beatriz García 2, 3 , Carla Martín 2, 3 , Helena Ordiales 2 , Olivia García-Suárez , Kelvin M Piña-Batista 4 , Jesús Merayo-Lloves 3 , Luís M Quirós 2, 3 , Iván Fernández-Vega 1, 3, 5, 6
Affiliation  

Previous studies have reported that heparan sulfate proteoglycans (HSPGs) promote amyloid-beta peptide and tau fibrillization in Alzheimer disease (AD) and provide resistance against proteolytic breakdown. We compared the expression levels of 17 HSPG core proteins in 18 AD cases and 6 controls. RT-PCR was used to analyze transcription levels. Immunohistochemistry was performed to localize HSPGs in the brain tissue. We detected expression of all HSPG genes investigated. SDC1, GPC3, and CD44v3 showed the lowest levels of expression, while SDC3 and GPC1 showed the highest. Remarkably, SDC4 and SRGN were overexpressed in most of the areas analyzed. Immunohistochemistry revealed the presence of both SDC4 and SRGN mostly associated with tau and amyloid-β pathology throughout the AD brains. In conclusion, in view of the involvement of HSPGs in AD pathology, especially SDC4 and SRGN, there would seem to be a relationship between the regulation of core protein expression and the pathological features suggesting HSPGs are potential inducers of the disease.

中文翻译:

硫酸乙酰肝素蛋白聚糖在阿尔茨海默病大脑中经历差异表达变化

以前的研究报告说,硫酸乙酰肝素蛋白聚糖 (HSPGs) 促进阿尔茨海默病 (AD) 中的淀粉样蛋白-β 肽和 tau 原纤维化,并提供对蛋白水解分解的抵抗力。我们比较了 18 例 AD 病例和 6 例对照中 17 种 HSPG 核心蛋白的表达水平。RT-PCR 用于分析转录水平。进行免疫组织化学以定位脑组织中的 HSPG。我们检测到所有研究的 HSPG 基因的表达。SDC1GPC3CD44v3的表达水平最低,而SDC3GPC1的表达水平最高。值得注意的是,SDC4SRGN在大多数分析的区域中过度表达。免疫组织化学显示 SDC4 和 SRGN 的存在主要与整个 AD 大脑中的 tau 和淀粉样蛋白-β 病理学相关。总之,鉴于 HSPGs 参与 AD 病理学,特别是 SDC4 和 SRGN,核心蛋白表达的调节与病理特征之间似乎存在关系,表明 HSPGs 是该疾病的潜在诱导剂。
更新日期:2020-04-17
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