Epigenetic regulation of IGF2/IGFBP7 signalling in anxiety disorders and neurodegenerative diseases

焦虑障碍（PTSD）和神经退行性疾病（阿尔茨海默病）是我们社会日益严重的问题。这些疾病的潜在分子机制尚不清楚。这两种疾病都与严重的认知障碍有关。此外，创伤后应激障碍和淀粉样蛋白病理也是与年龄相关的认知能力下降（或痴呆）的危险因素。最近的研究表明，这两种风险因素之间存在联系，可能会加速痴呆症的进展。然而，这种联系的性质仍不清楚。最近的出版物和我们实验室的数据表明，IGF信号的表观遗传基因调控(例如。IGF2/IGFBP7)可能在恐惧消退和年龄相关的记忆障碍中起重要作用。其他人和我们已经提出针对IGF2信号和成人神经发生的治疗策略可能适合治疗这些疾病。因此，了解IGF信号的这种表观遗传调控的本质是至关重要的。我的研究将结合多种方法，如分子、药理学、组织学和行为技术在疾病动物模型中。阵列和高通量测序技术的使用也将有助于筛选与年龄相关的认知疾病的潜在生物标志物和治疗靶点。

Anxiety disorders (PTSD) and neurodegenerative diseases (Alzheimers disease) are an increasing problem to our societies. The underlying molecular mechanisms of such diseases are only poorly understood. Both diseases are associated with a severe cognitive impairment. Moreover, PTSD and amyloid pathology are also risk factors for age-related cognitive decline (or dementia). Recent studies suggest a bond between both risk factors that could accelerate the progression of dementia. However, the nature of this bond is still unclear. Recent publications and data from our lab indicate that epigenetic gene regulation of IGF signaling (eg. IGF2/IGFBP7) might play an important role in fear extinction and age-associated memory impairment. Others and we have suggested that therapeutic strategies that target IGF2 signaling and adult neurogenesis might be suitable to treat these diseases. Therefore, to understand the nature of such epigenetic regulation of IGF signaling is crucial. My research would combine multiple approaches such as molecular, pharmacological, histological, and behavioral techniques in disease animal models. The use of array and high-throughput sequencing technologies will also help to screen for potential biomarkers and therapeutic targets for age-associated cognitive diseases.