Alzheimer's disease is a progressive neurodegenerative disorder characterized by extracellular accumulation of amyloid-beta (Aβ) peptide, which induces synaptic dysfunction, alteration of intracellular signaling pathways, hyperphosphorylation of the Tau protein, and cognitive impairment. Genistein, one of the major isoflavones present in soy and soy products, has been shown to modulate some of the pathogenic events associated with the neurodegeneration process. However, its underlying mechanisms remain to be clarified. Therefore, the objectives of the present study were to evaluate the ability of genistein to protect against Aβ_1–42-induced cognitive impairment in rats and to elucidate some of the possible mechanisms involved in its neuroprotective effects in the hippocampus. Male Wistar rats received bilateral intracerebroventricular infusions of Aβ_1–42 (2 nmol) and genistein 10 mg/kg orally for 10 days. The Aβ-infused animals showed significant impairment of memory, which was accompanied by the following neurochemical alterations in the hippocampus: decreased levels of the synaptic proteins synaptophysin and postsynaptic density protein 95 (PSD-95), hyperphosphorylation of Tau with increased activation of glycogen synthase kinase-3β and c-Jun N-terminal kinase, and inactivation of ERK. Treatment with genistein improved Aβ-induced cognitive impairment by attenuation of synaptotoxicity, hyperphosphorylation of Tau, and inactivation of ERK. Furthermore, treatment with this soy isoflavone did not cause systemic toxicity. These findings provide further evidence of the neuroprotective effect of genistein in an in vivo model of Aβ toxicity and, importantly, extend the current knowledge concerning the mechanisms associated with the neuroprotective effects of this compound in the hippocampus.

阿尔茨海默病是一种进行性神经退行性疾病，其特征是淀粉样蛋白 β (Aβ) 肽的细胞外积聚，从而导致突触功能障碍、细胞内信号通路的改变、Tau 蛋白的过度磷酸化和认知障碍。染料木素是大豆和豆制品中存在的主要异黄酮之一，已被证明可以调节与神经变性过程相关的一些致病事件。然而，其潜在机制仍有待阐明。因此，本研究的目的是评估染料木黄酮对 Aβ _{1-42 的}保护能力。诱导大鼠认知障碍，并阐明其在海马中的神经保护作用所涉及的一些可能机制。雄性 Wistar 大鼠接受双侧脑室内输注 Aβ _1-42(2 nmol) 和染料木黄酮 10 mg/kg 口服 10 天。注入 Aβ 的动物表现出显着的记忆障碍，伴随着海马体的以下神经化学变化：突触蛋白突触素和突触后密度蛋白 95 (PSD-95) 水平降低，Tau 过度磷酸化，糖原合成酶激活增加激酶-3β 和 c-Jun N 端激酶，以及 ERK 的失活。用染料木黄酮治疗通过减弱突触毒性、Tau 过度磷酸化和 ERK 失活来改善 Aβ 诱导的认知障碍。此外，用这种大豆异黄酮处理不会引起全身毒性。这些发现为染料木黄酮在体内的神经保护作用提供了进一步的证据。 Aβ 毒性模型，重要的是，扩展了当前关于与该化合物在海马中的神经保护作用相关的机制的知识。