PQ6: Lipocalin-2 as a therapeutic target for prevention of cancer cachexia

项目总结： 慢性系统性红斑狼疮患者常见的疾病行为、代谢紊乱和认知能力下降。 疾病，并对生活质量和最终生存作出重大贡献。其他由疾病引起的疾病 包括厌食症和嗜睡也会影响患者从救命或延长生命中恢复的能力。 干预，减少积极与潜在疾病作斗争的动力。虽然 癌症患者的恶病质早在两千多年前就有描述，其核心机制 人们对这种疾病的潜在原因知之甚少。此外，目前还没有有效的药物。 治疗。认知功能减退在所有慢性病中都很常见，也可能是癌症患者的主要症状。 患者，甚至在开始治疗之前。我们的实验室致力于解开基本的机制 癌症引发神经炎症，这是患者恶病质和认知功能下降的关键驱动因素 癌症。在这项提案中，我们将重点了解系统性疾病的范围和机制 诱导产生一种名为Lipocalin-2的分子，该分子反过来作用于大脑，导致食欲不振 和认知能力下降。这项提议的意义在于它将我们的历史焦点独特地结合在一起 关于神经内分泌学和神经炎症，以及针对理解的新的合作和努力 癌症患者厌食和神经认知功能下降的程度和机制。长期目标 我们研究的重点是从机制上理解急性疾病的反应以及它是如何转变的。 所有癌症类型的慢性神经炎，以开发更有效的治疗干预措施。

Project Summary: Illness behaviors, metabolic disturbances, and cognitive decline are common in patients with chronic systemic diseases, and contribute substantially to quality of life and ultimate survival. Other illness-induced morbidities including anorexia and lethargy also compromise the ability of patients to recover from life-saving or extending interventions, and diminish the motivational drive to aggressively battle the underlying condition. Although cachexia in cancer patients was described more than two thousand years ago, the central mechanisms underlying this disorder are poorly understood. Furthermore, there is currently no effective pharmaceutical treatment. Cognitive decline is common in all chronic diseases, and can be a presenting complaint in cancer patients, even prior to initiation of therapy. Our laboratory is dedicated to unraveling the basic mechanisms whereby cancer triggers neuroinflammation, a key driver of cachexia and cognitive decline in patients with cancer. In this proposal, we will focus on understanding the scope and mechanism by which systemic illness induces the production of a molecule called lipocalin-2, that in turn acts on the brain to cause loss of appetite and cognitive decline. The significance of this proposal resides in its unique combination of our historical focus on neuroendocrinology and neuroinflammation, with new collaborations and efforts directed at understanding the extent and mechanisms of anorexia and neurocognitive decline in patients with cancer. The long-term goal of our research is to gain mechanistic understanding of the acute illness response and how it is transitioned into chronic neuroinflammation in all cancer types, in order to develop more effective therapeutic interventions.