在神经退行性疾病中的TREM2:突变谱,病理生理学和治疗向
Hyewon Yang1, Danyeong Kim1,2, YoungSoon Yang3
1Department of Bionano Technology, Gachon University, Seongnam 13120, Republic of Korea.
International journal of molecular sciences
|August 14, 2025
概括
在骨髓细胞2 (TREM2) 上表达的触发受体对大脑免疫细胞功能至关重要,并与神经退行性疾病有关. TREM2突变会损害微质活动,恶化疾病,但新的疗法旨在恢复功能.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 遗传学 是一个遗传学.
背景情况:
- TREM2 (在骨髓细胞2表达的触发受体) 是中枢神经系统中的一个关键的微质受体.
- 它调节关键功能,包括免疫反应,细胞化和脂质代谢.
- 功能障碍的TREM2涉及神经退行性疾病,如阿尔茨海默氏症,前性痴呆症和帕金森病.
研究的目的:
- 审查TREM2的结构,功能以及其致病变体的影响.
- 探索TREM2突变的分子和细胞后果.
- 突出针对神经退行性疾病TREM2信号的新兴治疗策略.
主要方法:
- 对TREM2结构,功能和相关疾病的文献综述.
- 对已知TREM2致病变体 (例如Arg47His,Arg62His) 的分子和细胞影响的分析.
- 目前和正在发展的治疗方法的概述,包括抗体和基因疗法.
主要成果:
- TREM2突变损害了微质激活,粉样聚合物的清除,并促进神经炎症.
- 确定的后果包括改变联体结合,蛋白质贩运,增加脱落和失调的信号传递.
- 在临床前研究中,各种治疗策略在恢复微质功能方面表现有前途.
结论:
- TREM2在神经保护中起着至关重要的作用,其功能障碍加剧了神经退行.
- 对TREM2信号的治疗调节为治疗神经退行性疾病提供了潜力.
- 临床成功取决于解决疾病异质性和突变特异性反应,优化时间和剂量.
相关概念视频
Parkinson's Disease: Overview
704
Neurodegenerative disorders are progressive diseases that cause irreversible damage and loss to neurons in specific brain areas. Examples of these disorders include Parkinson's disease, Alzheimer's disease, Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS). These disorders share characteristics such as proteinopathies, selective neuronal vulnerability, and a complex interplay between genetic and environmental factors. The primary therapeutic goal for these conditions is...
704
Enzyme-linked Receptors
80.0K
Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
80.0K
Alzheimer's Disease: Treatment
261
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...
261
Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein
448
Antiepileptic drugs, such as levetiracetam (Keppra) and brivaracetam (Briviact), have emerged as crucial tools in managing epilepsy. These medications exert their therapeutic effects by targeting the synaptic vesicle protein SV2A, a transmembrane glycoprotein primarily found in the brain.
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
448
Alzheimer's Disease: Overview
668
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...
668
Psychosis: Pathophysiology of Schizophrenia and Other Psychotic Disorders
957
Schizophrenia is a neurodevelopmental disorder whose origins are rooted in complex genetic components. Despite our burgeoning understanding, the pathophysiology of this disorder remains incompletely deciphered.
Researchers have identified genetic factors that increase susceptibility to schizophrenia, underscoring the intricate interplay between genetics and environment in disease development. At the core of schizophrenia's pathophysiology is excessive dopaminergic neurotransmission within...
Researchers have identified genetic factors that increase susceptibility to schizophrenia, underscoring the intricate interplay between genetics and environment in disease development. At the core of schizophrenia's pathophysiology is excessive dopaminergic neurotransmission within...
957


