神经退行性疾病，包括常见的阿尔兹海默症及痴呆，帕金森病及较少见的脊髓侧束硬化症和亨廷顿舞蹈症等，已逐渐成为影响人类健康的杀手。由于慢性及不可逆的特征，这些脑变性疾病对病人家庭、社会造成巨大的负担。然而，目前的治疗方法还只停留在有限的症状控制。对多数退行性疾病无药可用。因此，寻找对退行性疾病有效的治疗手段是各国科研及药物研发界的重要导向。此项研究拟运用细胞、线虫和果蝇多种模式和创新技术对突触蛋白SCAMP5在神经退行性疾病进程中的表达和作用进行深入研究。基于我们大量的前期工作，我们将探讨SCAMP5在自噬、神经毒性蛋白传播这两个神经变性疾病新机制中的作用及机理。我们假设是SCAMP5是一个在病理状态下受诱导的对自噬有抑制作用的，同时促进神经毒性蛋白分泌的细胞毒性辅助因子。这是一个在前沿领域对一个潜在的疾病调控蛋白的功能研究。结果将可能会对对神经变性疾病的治疗提供新的思路和靶点。

Due to increased longevity, neurodegenerative diseases, which include the common Alzheimer and Parkinson diseases, and the less common amyotrophic lateral sclerosis (ALS) and Huntington disease, have become major factors affecting public health. Because of the chronic and irreversible nature of these disorders, neurodegenerative diseases have grown to a huge financial burden to the affected families and societies, and have taken enormous emotional toll on the family members of the patients. Unfortunately, current treatment options are limited to symptom management. There is no cure for these diseases. Thus, there is a pressing need for the research community and pharmaceutical industry to develop novel disease-modifying therapeutics for neurodegenerative diseases. In this proposal, we will study the expression and function of a synaptic protein, SCAMP5, during neurodegeneration using cellular, C. elagans, and drosophila models and a variety of novel techniques. Our preliminary studies have suggested that SCAMP5 as a potentially important regulator for autophagy and the transmission of neurotoxic proteins, and these two mechanisms will be the main focus of our investigation. We hypothesize that SCAMP5 is a novel regulator of autophagy and neurotoxic protein transmission, and is induced during pathological conditions. Therefore，this study will shed light on the regulation of two important disease-causing mechanisms, autohphagy and toxic protein transmission, by a synaptic protein. The results from our study will generate new insights into the disease treatment.