Novel cognitive enhancing strategies for Alzheimer's disease

阿尔茨海默病的新认知增强策略

• 批准号: 2106048
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2106048
• 关键词: Novel; cognitive; enhancing; strategies; Alzheimer

Alzheimer's disease (AD), the major age-related form of dementia, is characterised by cognitive dysfunction. Strategies to enhance cognition could impact on quality of life for a significant proportion of our ageing population. In AD the transmembrane amyloid precursor protein (APP) is proteolytically cleaved to generate the neurotoxic amyloid-beta. However, under normal circumstances APP is cleaved to generate soluble APP (sAPP) that has neuroprotective and cognitive-enhancing effects which are mediated by sAPP binding to an unknown receptor on the surface of neurons. The objectives of this proposal are to take the essential next steps in exploring the cognitive enhancing potential of sAPP by: 1) identifying the receptor and binding partners for sAPP on the surface of neuronal cells; and 2) validating the identified receptor in sAPP's actions on synaptic plasticity and protection against oxidative stress. A range of biochemical, biophysical and cell biological approaches will be employed, including focused studies on human induced-pluripotent stem cell (iPSC)-derived neurons. Identification of the sAPP receptor and its binding partners will open the way to novel pharmacological approaches to mimic sAPP activity in AD.

阿尔茨海默病（AD）是与年龄相关的主要痴呆症形式，其特征是认知功能障碍。提高认知能力的策略可能会对很大一部分老龄化人口的生活质量产生影响。在阿尔茨海默病中，跨膜淀粉样蛋白前体蛋白（APP）被蛋白水解裂解以产生神经毒性淀粉样蛋白- β。然而，在正常情况下，APP被裂解产生可溶性APP (sAPP)，具有神经保护和认知增强作用，这是由sAPP与神经元表面的未知受体结合介导的。本研究的目的是通过：1)在神经元细胞表面识别sAPP的受体和结合伙伴；2)验证所鉴定的受体在sAPP突触可塑性和抗氧化应激中的作用。将采用一系列生化、生物物理和细胞生物学方法，包括对人类诱导多能干细胞（iPSC）衍生神经元的重点研究。识别sAPP受体及其结合伙伴将开辟新的药理学方法来模拟sAPP在AD中的活性。