Autophagy-Enhancers to reduce sleep disturbances: a combined approach
自噬增强剂减少睡眠障碍:综合方法
基本信息
- 批准号:508402643
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Research Grants
- 财政年份:
- 资助国家:德国
- 起止时间:
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Alzheimer's disease (AD) is a progressive neurodegenerative disease that leads to devastating cognitive impairment. To date, the complex pathophysiology underlying AD is not fully understood. However, it is known that insomnia is a risk factor for AD and that sleep disturbances are an early component of AD. Sleep is essential for memory consolidation. An important neurophysiological mechanism related to declarative memory consolidation is slow-wave sleep (SWS). Patients with mild cognitive impairment (MCI) or dementia due to AD are characterized by a more rapid decline in the proportion of SWS compared with individuals of the same age without neurodegenerative disease. In addition, studies have shown that age-related sleep disorders are associated with decreased insulin sensitivity and impaired neuropeptide Y (NPY) signaling. Due to the difficulty to develop curative therapies in the dementia stage, the focus of therapy research for AD has in part shifted to the early stages, i.e., finding disease-modifying agents and interventional approaches to maintain brain health and cognitive performance in the MCI stage or even earlier. One promising disease-modifying agent may be the polyamine spermidine. Previous research has shown that increased exogenous spermidine benefits various aspects of general health, T-cell function, and memory maintenance in aging animals and humans. Additionally, spermidine supplementation (Spd-S) was found to protect against age-related changes in sleep patterns in Drosophila fruit flies. However, to date, it is not known whether the beneficial effects of spermidine on brain health are mediated (in part) by changes in sleep quality and associated changes in insulin-glucose metabolism. The goal of the proposed project is to determine the effects of Spd-S on sleep physiology and sleep-dependent memory consolidation. In addition, the mechanisms underlying this relationship will be systematically investigated in both fly models and humans, particularly insulin-glucose metabolism, NPY signaling, and the relationship with markers of autophagy. In animal models, the role of autophagy in sleep control will be genetically tested in middle-aged, old and AD flies. In addition, the metabolic changes responsible for the sleep protective effect of Spd-S will be investigated. In humans, an intervention study will investigate the ability of Spd-S to improve SWS and sleep-related memory consolidation in MCI compared to placebo supplementation. The proposed project will provide insight into the potential relationship between Spd-S, cell autonomous mechanisms such as autophagy, non-cell autonomous mechanisms such as NPY, sleep and memory. Moreover, improvement of sleep physiology and memory consolidation via Spd-S might lead to clinically relevant preservation of brain health in aging.
阿尔茨海默病 (AD) 是一种进行性神经退行性疾病,会导致严重的认知障碍。迄今为止,AD 背后复杂的病理生理学尚未完全了解。然而,众所周知,失眠是 AD 的危险因素,而睡眠障碍是 AD 的早期组成部分。睡眠对于巩固记忆至关重要。与陈述性记忆巩固相关的一个重要的神经生理学机制是慢波睡眠(SWS)。与没有神经退行性疾病的同龄个体相比,患有轻度认知障碍(MCI)或 AD 所致痴呆的患者的特征是 SWS 比例下降更快。此外,研究表明,与年龄相关的睡眠障碍与胰岛素敏感性下降和神经肽 Y (NPY) 信号传导受损有关。由于痴呆阶段很难开发出治愈性疗法,AD治疗研究的重点已部分转移到早期阶段,即在MCI阶段或更早寻找疾病缓解剂和介入方法来维持大脑健康和认知能力。一种有前途的疾病缓解剂可能是聚胺亚精胺。先前的研究表明,增加外源性亚精胺有益于衰老动物和人类的整体健康、T 细胞功能和记忆维持的各个方面。此外,还发现补充亚精胺(Spd-S)可以防止果蝇睡眠模式与年龄相关的变化。然而,迄今为止,尚不清楚亚精胺对大脑健康的有益作用是否(部分)是通过睡眠质量的变化以及胰岛素-葡萄糖代谢的相关变化来介导的。该项目的目标是确定 Spd-S 对睡眠生理学和睡眠依赖性记忆巩固的影响。此外,还将在果蝇模型和人类中系统地研究这种关系的机制,特别是胰岛素-葡萄糖代谢、NPY信号传导以及与自噬标记物的关系。在动物模型中,自噬在睡眠控制中的作用将在中年、老年和 AD 果蝇中进行基因测试。此外,还将研究与 Spd-S 的睡眠保护作用相关的代谢变化。在人类中,一项干预研究将调查与安慰剂补充剂相比,Spd-S 改善 MCI 中 SWS 和睡眠相关记忆巩固的能力。拟议的项目将深入了解 Spd-S、细胞自主机制(如自噬)、非细胞自主机制(如 NPY、睡眠和记忆)之间的潜在关系。此外,通过 Spd-S 改善睡眠生理和记忆巩固可能会导致临床相关的衰老过程中大脑健康的保存。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Professorin Dr. Agnes Flöel其他文献
Professorin Dr. Agnes Flöel的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Professorin Dr. Agnes Flöel', 18)}}的其他基金
TDCS-enhanced training in chronic post-stroke aphasia
TDCS 强化训练治疗慢性卒中后失语症
- 批准号:
371431740 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Clinical Trials
Mechanisms of action of oscillatory transcranial direct current stimulation during sleep on electrophysiological correlates and memory consolidation – assessed via presurgically implanted electrodes in patients with epilepsy
睡眠期间振荡经颅直流电刺激对电生理相关性和记忆巩固的作用机制 â 通过术前植入的电极对癫痫患者进行评估
- 批准号:
413459402 - 财政年份:2019
- 资助金额:
-- - 项目类别:
Research Grants
Cognitive improvement after bariatric surgery in obesity: neuronal correlates and underlying mechanisms
肥胖症减肥手术后的认知改善:神经元相关性和潜在机制
- 批准号:
329488092 - 财政年份:2017
- 资助金额:
-- - 项目类别:
Research Grants
Mechanisms underlying atDCS-effects in patients with recurrent traumatic brain injury - a multi-modal analysis using electrophysiology, MR-spectroscopy and functional MRI
复发性创伤性脑损伤患者 atDCS 效应的潜在机制 - 使用电生理学、MR 能谱和功能 MRI 的多模态分析
- 批准号:
240331393 - 财政年份:2013
- 资助金额:
-- - 项目类别:
Research Grants
Einfluss transkranieller Gleichstromstimulation auf Gedächtniskonsolidierung und neuronale Strukturen bei Patienten mit "Mild Cognitive Impairment"
经颅直流电刺激对“轻度认知障碍”患者记忆巩固及神经元结构的影响
- 批准号:
222159376 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Research Grants
Lässt sich die Gedächtnisbildung bei Menschen in höherem Lebensalter verbessern durch eine Ernährungsmodifikation? Wenn ja, welche Mechanismen liegen diesem Effekt zugrunde?
通过饮食调整可以改善老年人的记忆形成吗?
- 批准号:
130538578 - 财政年份:2009
- 资助金额:
-- - 项目类别:
Research Grants
Does dopaminergic neuromodulation enhance procedural motor learning an activities of daily living in healthy elderly subjects and in patients with chronic motor deficits after stroke? Which mechanisms underlie the enhancement?
多巴胺能神经调节是否能增强健康老年受试者和中风后慢性运动缺陷患者的程序性运动学习和日常生活活动?
- 批准号:
18080661 - 财政年份:2005
- 资助金额:
-- - 项目类别:
Research Grants
Episodic encoding and retrieval. A study with transcranial magnetic stimulation
情景编码和检索。
- 批准号:
5365901 - 财政年份:2002
- 资助金额:
-- - 项目类别:
Research Fellowships
Neuromodulation through brain stimulation-assisted cognitive training in patients with post-chemotherapy cognitive impairment (Neuromod-PCCI): an explorative proof-of-concept randomized sham-controlled double-blind feasibility phase II trial
通过脑刺激辅助认知训练对化疗后认知障碍患者进行神经调节 (Neuromod-PCCI):一项探索性概念验证随机假手术对照双盲可行性 II 期试验
- 批准号:
517737874 - 财政年份:
- 资助金额:
-- - 项目类别:
Clinical Trials
相似海外基金
Pathophysiology of osteoarthritis focusing on transcriptional enhancers from GWAS and single cell RNAseq analysis
骨关节炎的病理生理学重点关注 GWAS 和单细胞 RNAseq 分析中的转录增强子
- 批准号:
23K08697 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Grant-in-Aid for Scientific Research (C)
Development of Nav1.1 Enhancers to Treat Alzheimer's Disease
开发 Nav1.1 增强剂来治疗阿尔茨海默病
- 批准号:
10801495 - 财政年份:2023
- 资助金额:
-- - 项目类别:
1/2 Discovery and validation of neuronal enhancers associated with the development of psychiatric disorders
1/2 与精神疾病发展相关的神经元增强剂的发现和验证
- 批准号:
10801125 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Impact of novel enhancers on Igh repertoire diversity
新型增强子对 Igh 库多样性的影响
- 批准号:
10716628 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Roles for uniquely human enhancers in brain development and WNT signaling
人类独特的增强子在大脑发育和 WNT 信号传导中的作用
- 批准号:
10577092 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Evaluating the Impact of Mutations in Distant-Acting Enhancers in Structural Birth Defects
评估远效增强子突变对结构性出生缺陷的影响
- 批准号:
10826564 - 财政年份:2023
- 资助金额:
-- - 项目类别:
Axon Regeneration-Associated Gene Enhancers Promoting Successful CNS Nerve Regeneration
轴突再生相关基因增强剂促进中枢神经系统神经再生成功
- 批准号:
10511016 - 财政年份:2023
- 资助金额:
-- - 项目类别:
NSF Postdoctoral Fellowship in Biology FY 2021: Deciphering grammatical rules of notochord enhancers and their role in notochord development in Ciona intestinalis
2021 财年 NSF 生物学博士后奖学金:破译脊索增强子的语法规则及其在海鞘脊索发育中的作用
- 批准号:
2109907 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Fellowship Award
New Collagen Reporters to characterise the effects of stressors and enhancers on skin aging
新的胶原蛋白记者来描述压力源和增强剂对皮肤衰老的影响
- 批准号:
2748730 - 财政年份:2022
- 资助金额:
-- - 项目类别:
Studentship
Systematic identification of enhancers to target the breadth of excitatory and inhibitory neuronal cell types in the cerebral cortex
系统鉴定增强剂以靶向大脑皮层兴奋性和抑制性神经元细胞类型的广度
- 批准号:
10512459 - 财政年份:2022
- 资助金额:
-- - 项目类别: