Unidad de Regeneración Neural, Unidad Funcional de Investigación de Enfermedades Crónicas (UFIEC), Instituto de Salud Carlos III (ISCIII), 28222 Majadahonda, Spain.
Instituto de Investigación de Enfermedades Raras (IIER), Instituto de Salud Carlos III (ISCIII), 28222 Majadahonda, Spain.
Int J Mol Sci. 2022 May 22;23(10):5820. doi: 10.3390/ijms23105820.
Amyloid-β 40 peptides [Aβ1-40 (Aβ40)] are present within amyloid plaques in the brains of patients with Alzheimer's disease (AD). Even though Aβ peptides are considered neurotoxic, they can mediate many biological processes, both in adult brains and throughout brain development. However, the physiological function of these Aβ peptides remains poorly understood, and the existing data are sometimes controversial. Here, we analyze and compare the effects of monomeric Aβ40 on the biology of differentiating human neural stem cells (human NSCs). For that purpose, we used a model of human NSCs called hNS1. Our data demonstrated that Aβ40 at high concentrations provokes apoptotic cellular death and the damage of DNA in human NSCs while also increasing the proliferation and favors neurogenesis by raising the percentage of proliferating neuronal precursors. These effects can be mediated, at least in part, by β-catenin. These results provide evidence of how Aβ modulate/regulate human NSC proliferation and differentiation, suggesting Aβ40 may be a pro-neurogenic factor. Our data could contribute to a better understanding of the molecular mechanisms involved in AD pathology and to the development of human NSC-based therapies for AD treatment, since these results could then be used in diagnosing the disease at early stages and be applied to the development of new treatment options.
淀粉样蛋白-β 40 肽（Aβ1-40（Aβ40））存在于阿尔茨海默病（AD）患者大脑中的淀粉样斑块中。尽管 Aβ 肽被认为具有神经毒性，但它们可以在成人大脑和整个大脑发育过程中介导许多生物学过程。然而，这些 Aβ 肽的生理功能仍知之甚少，并且现有数据有时存在争议。在这里，我们分析和比较了单体 Aβ40 对分化的人类神经干细胞（hNSC）生物学的影响。为此，我们使用了一种称为 hNS1 的人类 NSC 模型。我们的数据表明，高浓度的 Aβ40 会在 hNSC 中引发细胞凋亡和 DNA 损伤，同时通过增加增殖神经元前体的比例来促进增殖和有利于神经发生。这些作用至少部分可以通过β-连环蛋白介导。这些结果提供了 Aβ 如何调节/调节人类 NSC 增殖和分化的证据，表明 Aβ40 可能是一种促神经发生因子。我们的数据可以帮助更好地理解 AD 病理涉及的分子机制，并为基于 hNSC 的 AD 治疗开发提供依据，因为这些结果可以用于在早期阶段诊断疾病，并应用于新的治疗方案的开发。
