基因突变 z-bo 2020-09-19 397

　　Recently, in a research paper published in the international journal Nature, researchers from Johns Hopkins University revealed how common genetic mutations cause brain damage-related amyotrophic lateral sclerosis (ALS) and frontotemporal Dementia (frontotemporal dementia, FTD), researchers said that changes in the C9orf72 gene located on human chromosome 9 will promote RNA molecules to block the key pathway of protein transport, thereby triggering molecular "traffic congestion" outside the nucleus of the brain, and then affecting the brain Normal function.

　　Researcher Dr. Jeffrey Rothstein pointed out that this common genetic mutation is related to 40% of hereditary ALS cases, 25% of hereditary FTD is directly related to the onset of the disease, and about 10% of non-hereditary two diseases are related. The main characteristics of ALS and FTD are that the nerve cells in the patient’s brain continue to degenerate over time. Taking FTD as an example, the damage can cause problems in the patient’s speech, language understanding and emotional processing. In ALS patients, degenerated neuronal cells It will affect the function of the spinal cord and brain, and the patient will eventually lose the ability to control muscles.

　　This gene mutation called C9orf72 does not modify the constituent elements of DNA, but causes a six-digit DNA nucleotide chain to repeat hundreds of thousands of times. Once the DNA mutation occurs, it will affect the cell to produce long RNA repeats. ; As early as 2013, researchers identified more than 400 special proteins in cells that repeated RNA chains can directly act on; and in this study, the researchers focused on a protein called RanGAP, which Proteins can mediate the effects of mutant RNA in cells.

　　In healthy cells, the protein RanGAP can transport molecules through the nuclear pore complex that connects the cytoplasm. The article uses human brain cells from the ALS-related C9orf72 mutation to study. The researchers found that the protein RanGAP is in a state of aggregation outside the nucleus. And the proteins that rely on RanGAP to transport into the nucleus will not flow through the nuclear pores. In another experiment, the researchers used Drosophila and human stem cells to conduct research. They added antisense oligonucleotides to block the interaction of antisense oligonucleotides with RanGAP, and then discovered the interfered nuclear pore complex. The body is starting to work again.

　　At present, researchers do not know the specific mechanism of gene C9orf72 mutation and cell death in the brain at each stage. Later, they hope to use more research to clarify why C9orf72 mutation can cause ALS and FTD.