The effect of juevnille protective programs on protein aggregation during aging

描述（由申请人提供）：许多迟发性神经退行性疾病，如亨廷顿氏病（HD）、阿尔茨海默病（AD）和肌萎缩侧索硬化症（ALS），都是由蛋白质的错误折叠和聚集引起的。这些疾病的最终风险因素是衰老。此外，在这些疾病中，易于聚集的蛋白质会影响神经元，随着疾病的发展，神经元会逐渐失去功能。患有这些疾病的人会出现与之相关的有害症状，如痴呆和运动功能丧失，最终死亡。目前，还没有治愈这些疾病的方法，只有很少的治疗方法可以减轻潜在的症状。最终，更创新的治疗方法的产生将是最重要的治疗，并希望治愈，并了解细胞和遗传途径参与保护蛋白质聚集将有助于。在神经退行性疾病中，易于聚集的蛋白在出生时表达，尽管疾病的症状直到生命后期才出现。此外，具有相同基因突变蛋白的个体在发病年龄上存在很大差异。这表明青少年项目的存在可以在以后的生活中保护一些有抵抗力的个体。研究人员一直在研究已知的保护途径，以避免或延迟蛋白质稳态（proteostasis）的失败，从而延迟或推断蛋白质聚集的毒性作用。这些方法已经找到了许多改善蛋白质平衡的方法，尽管往往有延迟发育和繁殖的风险。因此，本研究的目的是确定在幼年阶段起作用的途径

DESCRIPTION (provided by applicant): Many late-onset neurodegenerative diseases, such as Huntington's disease (HD), Alzheimer's disease (AD) and Amyotrophic Lateral Sclerosis (ALS), are caused by the misfolding and aggregation of proteins. The ultimate risk factor for these diseases is aging. Also, in these diseases aggregate-prone proteins affect neurons, which increasingly lose function as the disease advances with age. Individuals stricken with these diseases succumb to the detrimental symptoms associated with them, such as dementia and loss of motor function and ultimately death. Currently, there are no cures for these diseases, and only few treatments to reduce the underlying symptoms are available. Ultimately, the production of more innovative therapeutic approaches will be most important for treatment, and hopefully cure, and understanding of the cellular and genetic pathways involved with protection against protein aggregation will help. In neurodegenerative diseases the aggregation-prone proteins are expressed at birth, although symptoms of disease are not present until later in life. Also, there exists great variability in age of onset among individuals who have the same genetically mutated protein. This suggests the presence of juvenile programs that can protect some resistant individuals later in life. Researchers have been studying known protective pathways that avoid or delay the failure of protein homeostasis (proteostasis) and thus delay or deduce toxic effects of protein aggregation. These approaches have found many ways to improve proteostasis, although often at the risk for delaying development and reproduction. Therefore, the goal of this research is to identify the pathways that act during juvenile stages to protect against protein aggregation and are compatible with normal development, growth, and cellular signaling later in life. This will be accomplished by addressing the following questions: does transient passage through stress-resistant dauer stage protect against protein aggregation, and from phenotypes associated with proteotoxicity later in life? And ultimately, our goal is to identify the mechanisms that are protective during aging when activated in juveniles. Caenorhabditis elegans has a physiological protective program (dauer diapause) that is known to be stress-resistant and protected from aging. The above questions will be addressed by transiently activating dauer program early in life, subsequently allowing for normal development, and observing the effects of these treatments on protein aggregation and toxicity during aging.