Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Jewish Home of San Francisco, San Francisco, California, USA.
FASEB J. 2019 Jan;33(1):231-238. doi: 10.1096/fj.201801001. Epub 2018 Jun 20.
Exosomes derived from chondroitin sulfate proteoglycan (CSPG) 4 type neural precursor cells (CSPG4Es) were purified from human plasma by sequential immunoabsorption with anti-CSPG4 and anti-platelet growth factor receptor α mAb to characterize the potential in vivo roles of CSPG4 cells in neuronal repair. Hepatocyte growth factor, fibroblast growth factors (FGFs)-2 and -13, and type 1 insulin-like growth factor (IGF-1), which enhance neuronal survival and functions, were quantified in CSPG4E extracts. For CSPG4Es of 24 healthy control subjects, mean levels of hepatocyte growth factor, FGF-13, and IGF-1, but not FGF-2, were significantly higher by up to 7-fold than in their neuronal-derived exosomes, and mean levels of all 4 growth factors were significantly higher by up to 8-fold than in their astrocyte-derived exosomes. Mean CSPG4E levels of all growth factors were significantly lower in patients with mild Alzheimer disease (AD) ( n = 24) than in age- and sex-matched cognitively normal control subjects ( n = 24). Mean CSPG4E levels of all growth factors were also significantly lower in 15 patients at the stage of moderate dementia from AD (AD) and at their preclinical stage 3 to 8 yr earlier (AD), with no differences between values at stages AD and AD. Current findings suggest that CSPG4 cells export in exosomes higher levels of neurotrophic factors than neurons or astrocytes and that CSPG4E neurotrophic factors are diminished early in AD, with no significant progression of decreases later in the course.-Goetzl, E. J., Nogueras-Ortiz, C., Mustapic, M., Mullins, R. J., Abner, E. L., Schwartz, J. B., Kapogiannis, D. Deficient neurotrophic factors of CSPG4-type neural cell exosomes in Alzheimer disease.
外泌体来源于硫酸软骨素蛋白聚糖 (CSPG) 4 型神经前体细胞 (CSPG4Es)，通过顺序免疫吸附抗 CSPG4 和抗血小板生长因子受体 α mAb 从人血浆中纯化，以表征 CSPG4 细胞在神经元修复中的潜在体内作用。肝细胞生长因子、成纤维细胞生长因子 (FGFs)-2 和 -13 以及 1 型胰岛素样生长因子 (IGF-1) 被量化为 CSPG4E 提取物，这些因子可增强神经元的存活和功能。对于 24 名健康对照受试者的 CSPG4Es，肝细胞生长因子、FGF-13 和 IGF-1 的平均水平，而不是 FGF-2，高达 7 倍，明显高于其神经元衍生的外泌体，所有 4 种生长因子的平均水平高达 8 倍，明显高于其星形胶质细胞衍生的外泌体。与年龄和性别匹配的认知正常对照组相比，轻度阿尔茨海默病 (AD) (n = 24) 患者的 CSPG4E 中所有生长因子的平均水平显著降低。在 AD 中处于中度痴呆阶段的 15 名患者 (AD) 及其临床前阶段 3 至 8 年前 (AD)，所有生长因子的 CSPG4E 水平也显著降低，AD 和 AD 阶段之间无差异。目前的研究结果表明，CSPG4 细胞在其外泌体中分泌的神经营养因子水平高于神经元或星形胶质细胞，AD 早期 CSPG4E 神经营养因子减少，在病程后期没有明显的减少进展。-Goetzl, EJ、Nogueras-Ortiz, C、Mustapic, M、Mullins, RJ、Abner, EL、Schwartz, JB、Kapogiannis, D. CSPG4 型神经细胞外泌体中缺乏神经营养因子在阿尔茨海默病中的作用。
