Thank you very much for the invitation and for asking such important questions. Our research team has developed a new molecule called α5-PAM, which stands for α5 subunit positive allosteric modulator. In our experiments with aging mice, we found that this molecule significantly improves cognitive function, including memory and other routine functions. Additionally, we observed that α5-PAM has a positive impact on brain cells themselves, making them healthier. This is particularly beneficial in the context of aging, as there is a general loss of neurons and cells in the human population as well. However, with the chronic treatment we demonstrated, there is an increase in cellular health, which in turn leads to enhanced cognitive function.

The data we have shown in aging mice actually aligns with what we have observed in chronic stress models and in models of amyloid deposition that resemble what happens in Alzheimer's disease. Therefore, this finding potentially has significant implications for the treatment of cognitive dysfunction in different brain regions associated with neuronal loss and cognitive impairment.

我们的研究团队开发了一种新的分子——α5-PAM，也就是α5亚型正向变构调节剂。我们在衰老小鼠的实验中发现，这种分子能够显著改善它们的认知功能，包括记忆力和一些常规功能。此外，我们还观察到这种分子对脑细胞本身也有积极影响，使脑细胞更加健康。这种效果在衰老背景下是非常有益的，因为即使在人类群体中，也会出现神经元和细胞的普遍损失。但通过我们所展示的这种慢性治疗，细胞健康得到了提升，进而导致认知功能的增强。

我们现在在衰老小鼠中展示的数据，实际上与我们在小鼠慢性应激模型以及类似阿尔茨海默病的淀粉样蛋白沉积模型中所展示的数据是一致的。因此，我认为这一发现可能对治疗与神经元损失和认知功能障碍相关的大脑区域的认知功能障碍具有潜在的临床意义。

This is a very important question. When we try to translate findings from animal models to human applications, there are several critical factors to consider. First, we need to ensure that the target we are aiming for—the α5-GABA-A receptor—is homologous between species. Fortunately, in our case, the α5-GABA-A receptor protein in rodents is 99% similar to that in humans, and its distribution in the brain is highly consistent, located in the prefrontal cortex and hippocampus, which are key regions involved in cognitive regulation. This similarity crucial is for ensuring that the effects we demonstrate in animal models will likely be replicated in human participants.

Another critical aspect is ensuring that there are no side effects that might not be detected in animal models but could emerge in clinical populations. This is why we conduct Phase I and Phase II clinical trials in humans, to ensure that the drug, which has shown efficiency and low side effects in animal models, will also have low side effects in clinical populations and the general human population.

这是一个非常重要的问题。当我们试图将动物模型中的发现转化为人类应用时，确实有很多因素需要考虑。首先，我们需要确保我们所针对的目标——α5-GABA-A受体，在两种物种之间是同源的。幸运的是，在我们的研究中，啮齿类动物和人类的α5-GABA-A受体蛋白相似度高达99%，且在大脑中的分布也高度一致，都位于与认知调节密切相关的大脑区域，如前额叶皮层和海马体。这对我们来说是一个关键的积极因素，因为它确保了我们在动物模型中开发和展示的效果，有可能在人类参与者中也能取得类似的疗效。

然而，另一个非常关键的方面是在常规药物开发过程中，我们需要确保不会出现动物模型中未检测到但在临床人群中可能出现的副作用。这也是为什么我们在人类研究中会开展一期、二期临床试验，以确保我们研发的药物在动物模型中表现出高效且副作用低的特点，在临床人群和人类总体中也能保持低副作用

This is an excellent question. I believe there are two main promising research directions in the fields of mental and neurodegenerative diseases.

First, there is significant progress being made in diagnostics. We are seeing improvements in the early detection of brain disorders and neurodegenerative diseases, such as Alzheimer's, using blood-based biomarkers. There have also been advancements in MRI and PET brain imaging, as well as the use of artificial intelligence (AI) to analyze these data sets. These technologies offer new possibilities for early diagnosis and intervention.

Second, there is a growing focus on developing better treatments that are based on the underlying biology of brain disorders. Unlike in the past, when treatments were often discovered by chance, we now have a deeper understanding of the biological mechanisms behind these disorders, including brain circuitry, cellular microcircuits, and molecular mechanisms. By targeting these pathways more precisely, we have a greater chance of developing meaningful and efficacious treatments for people with brain disorders.

这是一个非常好的问题。我认为在精神和神经退行性疾病领域，有两个主要的研究方向非常有潜力。

首先，是关于诊断的新研究。我们已经看到了在脑部疾病和神经退行性疾病诊断方面的显著进步。例如，利用基于血液的生物标志物进行早期检测，以及更准确地检测患脑部疾病（包括阿尔茨海默病）的风险。最近的新闻中也报道了使用核磁共振成像（MRI）、正电子发射断层扫描（PET）脑成像技术，以及人工智能（AI）来帮助分析这些数据集。这些技术的发展为早期诊断和干预提供了新的可能性。

其次，是开发基于大脑疾病生物学原理的更好治疗方法。以前的治疗方法往往依赖于偶然发现，但如今我们对大脑疾病的生物学机制有了更深入的理解，包括大脑回路、细胞层面的微回路以及相关的分子机制。通过更精准地针对这些途径，我认为我们有更大的机会为脑部疾病患者开发出有意义且有效的治疗方法。