Alzheimer's Disease (AD) is the most common cause of dementia, affecting 25 million people worldwide. Accumulation of Amyloid-β (Aβ) in the mitochondria has been shown to adversely affect key enzymes including pyruvate dehydrogenase (PDH), succinate dehydrogenase (SDH), oxoglutarate dehydrogenase (OGDH). Accumulation of Aβ is also believed to increase Tau expression and pathology. Tau, in its toxic state, results in synaptic damage causing memory and cognitive dysfunction. We are developing a drug to treat AD namely AmyTrap. The active pharmacological ingredient is a retro inverso, Aβ-binding peptide which sequesters Aβ. We wanted to examine the effect of AmyTrap peptide on Aβ-induced mitochondrial dysfunction and Tau phosphorylation. Therefore, we treated SH-SY5Y neuroblastoma cells with wild-type Aβ, a mutant AβY10A, AmyTrap peptide (RI-peptide), or Aβ and RI-peptide for 72 h. The mutant AβY10A is known to impact the self-aggregating property of Aβ as this Tyr10 is essential for self-aggregation. As expected, AβY10A reversed PDH, OGDH and SDH dysfunction to near normal levels. Further, AβY10A successfully reversed Tau phosphorylation, suggesting that Tyr10 is also associated with Aβ-induced cytotoxicity. RI-peptide was able to significantly reverse SDH dysfunction with limited effect on PDH and Tau phosphorylation. The findings are suggestive that the Tyr10 on Aβ plays a critical role in the self-aggregation. Further studies are warranted to expand these findings.

中文翻译：

---

AmyTrap（一种淀粉样蛋白-β 结合药物）对培养的神经母细胞瘤细胞中 Aβ 诱导的线粒体功能障碍和 tau 磷酸化的影响。

阿尔茨海默病 (AD) 是导致痴呆症的最常见原因，影响着全球 2500 万人。线粒体中β淀粉样蛋白 (Aβ) 的积累已被证明会对关键酶产生不利影响，包括丙酮酸脱氢酶 (PDH)、琥珀酸脱氢酶 (SDH)、氧化戊二酸脱氢酶 (OGDH)。Aβ 的积累也被认为会增加 Tau 的表达和病理。Tau 蛋白处于有毒状态时，会导致突触损伤，从而导致记忆和认知功能障碍。我们正在开发一种治疗 AD 的药物，即 AmyTrap。活性药理学成分是一种逆向 Aβ 结合肽，可隔离 Aβ。我们想要研究 AmyTrap 肽对 Aβ 诱导的线粒体功能障碍和 Tau 磷酸化的影响。因此，我们用野生型 Aβ、突变型 AβY10A、AmyTrap 肽（RI 肽）或 Aβ 和 RI 肽处理 SH-SY5Y 神经母细胞瘤细胞 72 小时。已知突变体 AβY10A 会影响 Aβ 的自聚集特性，因为该 Tyr10 对于自聚集至关重要。正如预期的那样，AβY10A 将 PDH、OGDH 和 SDH 功能障碍逆转至接近正常水平。此外，AβY10A 成功逆转了 Tau 磷酸化，表明 Tyr10 也与 Aβ 诱导的细胞毒性有关。RI 肽能够显着逆转 SDH 功能障碍，但对 PDH 和 Tau 磷酸化的影响有限。研究结果表明 Aβ 上的 Tyr10 在自聚集中发挥着关键作用。需要进一步的研究来扩大这些发现。