肌肉萎缩性侧索硬化症,ALS,基因突变 z-bo 2020-09-23 468

　　According to the “Genetics” magazine of “Nature”, in North America and Europe, about 3% of patients with amyotrophic lateral sclerosis (ALS) have gene mutations related to multiple neuronal functions. This mutation is both non-familial and familial, making it the most common genetic cause of this disease. The study was jointly completed by Dr. John Landers, professor of neurology at the Worcester campus, and Dr. Jan Veldink of Utrecht University Medical Center, the Netherlands. The study was funded by the MinE project of the ALS Association, which is an international discovery of ALS genes. Cooperative project, fund donated by ALS ice bucket.

　　ALS is a progressive neurodegenerative disease that affects the functional activities of neurons in the brain and spinal cord. Eventually, ALS patients will lose the ability to initiate and control muscle movement, and usually develop general paralysis and death 2-5 years after diagnosis. However, 10% of ALS patients are familial, which means that this is a genetic disease. Another 90% of patients think it is non-hereditary or has no family history. However, most patients with ALS are likely to be directly or indirectly caused by genes.

　　ALS Association announced the establishment of the minE project in 2014, which is mainly to sequence at least 15,000 ALS patients worldwide. The project was originally initiated by the United States under the research results of Dr. Lander. The idea for the project came from Bernard Muller and Robbert Jan Stuit, two entrepreneurs suffering from ALS. After visiting the ALS Research Center in the Netherlands, they found an opportunity to accelerate genetic understanding of diseases. Thousands of DNA samples in the Dutch ALS Research Center were left unused due to the high cost of research.

　　"This research became possible with the cooperation of scientists." Landers said, "Its success comes from the joint efforts of scientists who are committed to finding the cause of ALS. This kind of collaborative research has expanded to more and more fields. ."

　　The results of this research come from more than 80 researchers in 11 countries. It is also the largest study of familial ALS in history. Exon data obtained from familial ALS samples have been uploaded to the ALS gene mutation server, which is a public database established by the ALS Association.

　　"The discovery of NEK1 highlights the value of big data in ALS research," said Lucie Bruijn of the ALS Association. "The large number of ALS samples makes it possible to obtain this discovery from complex genetic analysis. The ALS ice bucket challenge ensures that the ALS Association invests in the MinE project, and builds a large-scale reserve of ALS biological samples for precise research.

　　The new gene NEK1 was obtained from a full-gene scanning study of more than 1,000 ALS family members. The gene was also found in isolated populations in the Netherlands through different methods. The comparison of more than 13,000 non-familial ALS patients with the control group once again proved that the mutation rate of the same gene is too high. Variation in gene sequence will lead to loss of gene function. NEK1 has many functions in neurons, including maintaining the shape of the cytoskeleton and promoting the transmission of neurotransmitters. In addition, NEK1 can also regulate the function of mitochondrial membranes, provide energy for nerve cells, and participate in the DNA repair process. The terminal stages of these functions caused by any means will increase the risk of ALS.

　　The understanding of NEK1 in this disease provides important clues for new targeted therapies. The ALS Association is currently funding Landers and Dr. Catherine Lutz to develop a new type of mouse model to study the effect of loss of protein function in the process of ALS disease. Once these models are successfully developed, they will be quickly applied to a wide range of ALS research. These tools are very important for the development of ALS drugs.