核受体 Nr4a1 的逐渐减少调解了与年龄相关的认知衰退
Jiang Chen1,2,3,4, Zhi Zhang1,2,3,4, Ying Liu1,2,3,4
1Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
概括
核受体子家族4组A成员1 (Nr4a1) 随着年龄的增长减弱认知能力. 恢复大脑中的Nr4a1水平可能通过通过TrkB信号来增强突触功能来治疗与年龄相关的认知衰退.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 衰老研究研究 衰老研究
背景情况:
- 认知能力下降是衰老的一个常见方面.
- 核受体子家族4组A成员1 (Nr4a1) 在记忆中发挥作用.
- 与年龄相关的Nr4a1下降和认知障碍之间的确切联系尚不清楚.
研究的目的:
- 调查与年龄相关的Nr4a1减少在认知衰退中的作用.
- 阐明Nr4a1对认知和突触功能影响的分子机制.
主要方法:
- 定量PCR和免疫化学分析以评估Nr4a1的表达.
- 在小鼠中进行行为测试以评估认知功能.
- 补丁电生理学来检查突触功能.
- 对Nr4a1与TrkB促进体相互作用的分子分析.
主要成果:
- 人类外周血液单核细胞和小鼠海马CA1神经元中的Nr4a1水平随着年龄的增长而下降.
- 在小鼠海马CA1金字塔神经元中失去Nr4a1会损害认知和激发性突触功能.
- Nr4a1直接与TrkB促进体结合,增强其转录.
- 在老年小鼠中,Nr4a1的过度表达改善了认知功能,这种效应被TrkB抑制所削弱.
结论:
- 与年龄相关的Nr4a1的减少有助于认知能力下降和突触功能受损.
- Nr4a1通过上调TrkB表达来改善认知障碍.
- Nr4a1代表了对抗与年龄相关的认知缺陷的潜在治疗目标.
相关概念视频
Aging
49
Aging is a complex biological phenomenon influenced by various processes that affect cellular and systemic functions. Several prominent theories attempt to explain its mechanisms, highlighting cellular limitations, oxidative damage, and hormonal changes as central factors in aging.
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
49
Transducer Mechanism: Nuclear Receptors
1.3K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.3K
Cognitive Development During Adulthood
94
Cognitive development continues throughout adulthood, undergoing significant shifts across early, middle, and late stages. Individual transition occurs from adolescent idealism to pragmatic and adaptable thinking in early adulthood. During this period, individuals learn to integrate personal beliefs with the recognition that other perspectives are equally valid. Exposure to the complexities of modern society, diverse experiences, and higher education contribute to this adaptive thought process,...
94
Alzheimer's Disease: Overview
468
Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
468
Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists
122
Cognitive enhancers, also known as "smart drugs," are substances used to enhance memory, mental alertness, and concentration. These can be natural or synthetic and improve cognition in conditions like Alzheimer's disease (AD) and other neurodegenerative diseases. Some common examples include caffeine, amphetamines, methylphenidate, modafinil, arecoline, donepezil, vortioxetine, and piracetam. These enhancers work on the principle of synaptic plasticity and altered circuit function.
122
Alzheimer's Disease: Treatment
183
Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...
183


