Hypothalamic AgRP neurons are determinants of healthy lifespan and higher brain f

在晚发性慢性病是慢性病的后果这一概念的指导下， 各种组织的长期过度工作，具有遗传和表观遗传 脆弱性，我断言这是不同的细胞能量代谢 组织，决定他们的健康和长寿，因此， 整个有机体。根据我以前和正在进行的工作，我假设 下丘脑中的一小部分神经元，产生Agouti相关蛋白质 （AgRP），作为所有组织能量利用的主要调节剂，因此， 这些下丘脑神经元决定健康的组织功能和寿命。我们 将选择性地上调或下调下丘脑AgRP神经元的活性 并测试这些扰动对外周正常生理的影响， 组织和大脑。我认为外周组织的这些变化 改变AgRP神经元功能的功能将对更高的 大脑的功能，包括学习和记忆，以及大脑的能力， 在正常老化或 病理过程，如阿尔茨海默病和帕金森病。 这个项目是唯一适合NDPA计划，因为它是 非传统的，代表了生物医学研究的方法， 根本不存在这是一个高风险的途径，但如果成功，将有很大的好处， 它可以立即导致各种慢性疾病的新疗法。

Guided by the notion that late onset chronic diseases are the consequence of prolonged overworking of various tissues that have genetic and epigenetic vulnerabilities, I assert that it is the cellular energy metabolism of the different tissues that determines their health and longevity and consequently that of the entire organism. Based on my previous and ongoing work, I hypothesize that a small set of neurons in the hypothalamus, which produce Agouti-related protein (AgRP), act as the master regulator of energy utilization by all tissues, and hence, these hypothalamic neurons determine healthy tissue function and longevity. We will selectively up- or down-regulate the activity of hypothalamic AgRP neurons and test the effect of these perturbations on normal physiology of peripheral tissues and that of the brain. I suggest that these changes in peripheral tissue function by altered AgRP neuronal functioning will have critical impact on higher brain functions as well, including learning and memory and the ability of the brain to withstand stress during neurodegeneration induced either by normal aging or by pathological processes, such as Alzheimer¿s and Parkinson¿s disease. This project is uniquely suited for the NDPA program because it is unconventional and represents an approach in biomedical research that is nonexistent. It is a high risk avenue, but, if successful, would have great benefits in that it could immediately lead to novel treatments for various chronic diseases.