单基TYROBP删除是阿尔茨海默氏症疾病的新型风险因素
Henna Martiskainen1, Roosa-Maria Willman2, Päivi Harju2
1Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland. henna.martiskainen@uef.fi.
Molecular neurodegeneration
|April 29, 2025
概括
单基TYROBP删除会增加阿尔茨海默病 (AD) 和痴呆的风险. 这一发现揭示了TYROBP删除作为一种新的AD风险因素,并表明神经退行性疾病的新治疗点.
科学领域:
- 神经遗传学 神经遗传学
- 免疫学 免疫学 免疫学
- 痴呆症研究 痴呆症研究
背景情况:
- 双性TYROBP和TREM2变体导致纳苏-哈科拉疾病 (NHD).
- 类型TYROBP变异很少见,它们在神经退行症中的作用尚不清楚.
- 芬兰的人口历史丰富了创始突变,包括TYROBP删除导致NHD.
研究的目的:
- 研究单基TYROBP删除对神经退行性疾病风险的影响.
- 在芬兰人口中识别TYROBP删除载体.
- 阐明 TYROBP 删除效应背后的分子机制.
主要方法:
- 在FinnGen生物库 (520,210名参与者) 中使用代理标记物识别单基TYROBP删除载体.
- 组合基因组和健康登记数据.
- 在人类单细胞衍生微状细胞上进行了转录和蛋白质组分析.
主要成果:
- 单基TYROBP删除与阿尔茨海默病 (AD) 和痴呆症的风险增加和早期发病有关.
- 报告了第一例具有NHD类型骨囊的单样TYROBP缺失载体的病例.
- 单基除降低了DAP12蛋白水平,调高了炎症反应,并降低了微状细胞中未折叠的蛋白质反应.
结论:
- 甲状腺增生蛋白缺失是阿尔茨海默病和痴呆症的新型风险因素.
- 研究结果表明,TYROBP缺失会影响神经炎症和蛋白质平衡.
- 确定了与TYROBP功能障碍相关的神经退行性疾病的潜在治疗点.
相关概念视频
01:26Alzheimer's Disease: Overview
315
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...
315
01:00Enzyme-linked Receptors
75.9K
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...
75.9K
01:28Human Genetics
470
Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
The complex relationship between genetics and psychology is observable through common biological components such...
470
02:41Lethal Alleles
13.1K
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
13.1K
01:09Epistasis Analysis
4.8K
Although Mendel chose seven unrelated traits in peas to study gene segregation, most traits involve multiple gene interactions that create a spectrum of phenotypes. When the interaction of various genes or alleles at different locations influences a phenotype, this is called epistasis. Epistasis often involves one gene masking or interfering with the expression of another (antagonistic epistasis). Epistasis often occurs when different genes are part of the same biochemical pathway. The...
4.8K
01:20The Retinoblastoma Gene
4.0K
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.0K