红髓原体体突变导致神经退行性疾病
Elvira Mass1, Christian E Jacome-Galarza1, Thomas Blank2
1Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Nature
|August 31, 2017
概括
在巨细胞的胎儿前体突变引起神经退行. 抑制微质中的MAP激酶途径可以防止神经元死亡,为神经退行性疾病提供新的治疗策略.
科学领域:
- 神经科学
- 遗传学
- 细胞生物学
背景情况:
- 神经退行性疾病涉及渐进的神经元损失和质细胞激活,微质细胞的作用尚不清楚.
- 与BRAF (V600E) 突变相关的囊细胞突变表明骨髓细胞中的体质突变在神经退化中起作用.
- 微细胞源自不同的红髓原生细胞 (EMP),与造血干细胞分开.
研究的目的:
- 调查EMP中的体质BRAF (V600E) 突变是否会导致神经退行.
- 探索ERK激活的微质在神经退行性疾病中的作用.
- 确定神经退行性疾病的潜在治疗点.
主要方法:
- 在小鼠EMP中BRAF (V600E) 的马赛克表达.
- 对微质激活,神经炎症和神经退行标志物的分析.
- 评估神经行为缺陷和BRAF抑制的有效性.
主要成果:
- 在EMP中Mosaic BRAF ((V600E) 的表达导致了巨细胞的克隆扩张和严重的晚期神经退行.
- 在小鼠和人类囊细胞病患者中观察到ERK激活的微粒细胞积累.
- 神经行为缺陷,星质,粉样蛋白前体沉积,突触损失和神经元死亡是由ERK激活的微质引起的.
- 在小鼠模型中,抑制BRAF可以防止这些病态结果.
结论:
- 在EMP血统中的体质突变可能是囊细胞形成的原始细胞,并导致晚期的神经退行.
- 微质中MAP激酶通路的激活是神经退行的一个致病因素.
- 针对微质MAP激酶通路的激活为神经退行性疾病提供治疗潜力.
相关概念视频
Neural Regulation
43.6K
Digestion begins with a cephalic phase that prepares the digestive system to receive food. When our brain processes visual or olfactory information about food, it triggers impulses in the cranial nerves innervating the salivary glands and stomach to prepare for food.
43.6K
Differentiation of Common Myeloid Progenitor Cells
4.1K
Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
4.1K
Disorders of the Nervous Tissue
2.8K
Nervous tissue is a vital component of the human body's communication system, enabling us to perceive and respond to stimuli. However, like all other tissues, it is vulnerable to disorders and diseases that can significantly impact our neurological functioning.
Homeostatic Imbalances:
Alzheimer's disease manifests as a gradual decline in memory and cognitive abilities, attributed to the buildup of amyloid plaques and neurofibrillary tangles in the brain.
Parkinson's disease arises from the...
Homeostatic Imbalances:
Alzheimer's disease manifests as a gradual decline in memory and cognitive abilities, attributed to the buildup of amyloid plaques and neurofibrillary tangles in the brain.
Parkinson's disease arises from the...
2.8K
Mutations
94.9K
Overview
94.9K
Mutations
44.8K
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
44.8K
Cancers Originate from Somatic Mutations in a Single Cell
15.0K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
15.0K


