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

IGF2/IGFBP7 信号在焦虑症和神经退行性疾病中的表观遗传调控

• 批准号: 235374648
• 负责人: Professor Dr. André Fischer, since 7/2013
• 金额: --
• 依托单位: Standort Göttingen
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/235374648?language=en
• 关键词: Epigenetic; regulation; IGF2; IGFBP7; signalling

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.

焦虑症（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知之甚少。这两种疾病都与严重的认知障碍有关。此外，PTSD和淀粉样蛋白病理学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，这两种危险因素之间的联系可能会加速痴呆症的进展。然而，这种债券的性质仍不清楚。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，IGF 2/IGFBP 7）可能在恐惧消退和年龄相关记忆障碍中起重要作用。其他人和我们建议，针对IGF 2信号传导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信号传导的这种表观遗传调节的性质至关重要。我的研究将结合联合收割机多种方法，如在疾病动物模型的分子，药理学，组织学和行为学技术。使用阵列和高通量测序技术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。

项目成果

Insulin growth factor binding protein 7 is a novel target to treat dementia

• DOI: 10.1016/j.nbd.2013.09.011
• 发表时间: 2014-02-01
• 期刊: NEUROBIOLOGY OF DISEASE
• 影响因子: 6.1
• 作者: Agbemenyah, Hope Y.;Agis-Balboa, Roberto C.;Fischer, Andre
• 通讯作者: Fischer, Andre

HDAC1 links early life stress to schizophrenia-like phenotypes

• DOI: 10.1073/pnas.1613842114
• 发表时间: 2017-06-06
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Bahari-Javan, Sanaz;Varbanov, Hristo;Fischer, Andre
• 通讯作者: Fischer, Andre