Neuroprotective Effects of Polysaccharides from Wolfberry, the Fruits of Lycium barbarum, Against Homocysteine-induced Toxicity in Rat Cortical Neurons
Neuroprotective Effects of Polysaccharides from Wolfberry, the Fruits of Lycium barbarum, Against Homocysteine-induced Toxicity in Rat Cortical Neurons
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DOI：
10.3233/jad-2010-1280
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发表时间：
2010-01-01
影响因子：
4
通讯作者：
Chang, Raymond Chuen-Chung
中科院分区：
文献类型：
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作者：
Ho, Yuen-Shan;Yu, Man-Shan;Chang, Raymond Chuen-Chung
以往的临床和流行病学研究表明，血浆同型半胱氨酸（Hcy）水平升高增加阿尔茨海默病（AD）的风险。虽然其毒性的潜在机制是难以捉摸的，它已被证明，同型半胱氨酸通过诱导细胞凋亡，DNA片段化和tau蛋白过度磷酸化损伤神经元。枸杞（枸杞）是一种水果，在亚洲国家以其保护眼睛和抗衰老的特性而闻名。我们实验室以前的研究表明，枸杞多糖（LBA）具有保护神经元免受淀粉样β（A β）肽神经毒性的能力。我们假设枸杞的神经保护作用不仅限于A β，还可以提供对其他AD风险因素的保护。在这项研究中，我们的目的是阐明枸杞对Hcy诱导的神经元损伤的神经保护作用。我们的数据表明，LBA处理显着减弱Hcy诱导的原代皮层神经元细胞死亡和凋亡的LDH和caspase-3样活性测定证明。LBA还显著降低tau-1（Ser 198/199/202）、pS396（Ser 396）和pS214（Ser 214）表位处的Hcy诱导的tau磷酸化以及tau的切割。同时，我们还发现在所有检测时间点，不同处理组之间p-GSK 3 β（Ser 9/Tyr 216）的磷酸化水平保持不变。LBA处理抑制p-ERK和p-JNK的升高。总之，我们的数据表明，LBA对暴露于Hcy的皮质神经元产生神经保护作用。因此，LBA有可能成为预防AD的疾病调节剂。
Previous clinical and epidemiological studies have suggested that elevated plasma homocysteine (Hcy) levels increased the risk of Alzheimer's disease (AD). Although the underlying mechanisms of its toxicity are elusive, it has been shown that Hcy damages neurons by inducing apoptosis, DNA fragmentation, and tau hyperphosphorylation. Wolfberry (Lycium barbarum) is a fruit that is known for its eye-protective and anti-aging properties in Asian countries. Previous studies from our laboratory have demonstrated that polysaccharides derived from wolfberry (LBA) have the ability to protect neurons from amyloid-beta (A beta) peptide neurotoxicity. We hypothesize that the neuroprotective effects of wolfberry is not limited to A beta and can also provide protection against other AD risk factors. In this study, we aim to elucidate the neuroprotective effects of wolfberry against Hcy-induced neuronal damage. Our data showed that LBA treatment significantly attenuated Hcy-induced neuronal cell death and apoptosis in primary cortical neurons as demonstrated by LDH and caspase-3 like activity assay. LBA also significantly reduced Hcy-induced tau phosphorylation at tau-1 (Ser198/199/202), pS396 (Ser396), and pS214 (Ser214) epitopes as well as cleavage of tau. At the same time, we also found that the phosphorylation level of p-GSK3 beta (Ser9/Tyr 216) remained unchanged among different treatment groups at all detected time points. LBA treatment suppressed elevation of both p-ERK and p-JNK. In summary, our data demonstrated that LBA exerted neuroprotective effects on cortical neurons exposed to Hcy. Therefore, LBA has the potential to be a disease-modifying agent for the prevention of AD.