PNAS interpretation! The diabetes drug metformin or is expected to treat the most common amyotrophic lateral sclerosis of the spinal cord!

!--:pagetitle,2020 /PRNewswire/ -- Researchers have found that an FDA-approved diabetes drug or therapeutic lysergic spinal lateral sclerosis (ALS), a devastating neurological disorder that causes paralysis in the body; With the development of neuronal cell function in the spinal cord, motor neurons transmit signals from the brain to the muscles and allow the body to move, ALS induces the death of these motor neurons, resulting in the loss of the ability of patients to speak, eat, move and breathe, there are more than 30,000 ALS patients in the United States, patients are generally diagnosed with life expectancy of 2-5 years, and there is no effective cure for ALSThe author is a scientist engaged in family genetic neurological diseases, he has been trying to find ways to block ALS, and now their research team has obtained research or for the study of the C9orf72 gene mutation induced by the genetic ALS laid a certain foundation, C9orf72 gene located on chromosome 9, in addition to ALS, C9orf72 Mutations in the gene can also cause dementia, which can lead to apathy, loss of emotional control and cognitive decline, some patients with C9orf72 mutations will develop ALS, others will develop ethnopathy, and one group of patients will develop both diseases, known as C9-ALS/FTDPhoto Credit: Wikipedia.com Researchers focus on C9-ALS, the most common genetic ALS caused by the C9orf72 gene mutation, when six DNA letters of the component gene genetic code (GGGGCC) are Mutations occur when hundreds of additional repetitions occur, like a word repeated hundreds in the same sentence, and the genetic mutation that induces C9-ALS may be part of a larger family of diseases caused by similar extensions of shorter fragments of DNAThe researchers found a protein called RAN (repeat-related non-aug protein, which accumulates damage to these cells in neurons and other brain cells and causes disease, after researchers found RAN proteins in 10 different repetitive extended diseases, including Huntington's disease; In a recent study published in the international journal Proceedings of the National Academy of Sciences, researchers found a special cell switch that, when turned on, intercepts cells and promotes the cell's production of RAN proteins, which is turned on by RNA copies in dilated mutations, known as the protein kinase PathwayTurning off the protein kinase R pathway switch blocks the production of RAN proteins for multiple types of pathogenic repeated expansion, making the protein kinase R pathway a fatal weakness of RAN protein diseaseThe researchers say the FDA-approved diabetes drug metformin can improve the symptoms of the disease in mice with brittle X chromosomal syndrome, although the disease interferes with protein production in a completely different way, because metformin promotes the normalization of protein production in patients with brittle X chromosomal syndrome, perhaps in the same way as for RAN protein diseasesThe researchers then wanted to test whether metformin could lower the level of RAN protein, which the results showed was possible, and then found that metformin inhibited levels of protein kinase R, reducing the level of RAN protein in C9-ALS/FTD mice and improving disease symptomsIt may be effective for specific genetic forms of ALS and frontal temporal dementia, as mutations in the C9orf72 gene know about RAN proteins, while studies conducted by other researchers suggest that metformin may not be effective in treating mice that do not produce RAN proteins and suffer from different forms of ALSTypically, it takes a decade or more to move promising research from the laboratory to the clinic, which was introduced in France in 1957 and approved in the United States in 1995, and now widely used as a safe and effective type 2 diabetes drug with fewer side effects, so researchers can skip the very difficult drug development process and immediately test whether the benefits of metformin therapy in mouse therapy can also be found in patients with C9-ALSNow researchers have begun a phase 2 open-label trial to test the effectiveness of metformin in C9-ALS patients, in which everyone will receive the drug, and the researchers will test its treatment safety and whether it can reduce the levelof RAN protein in the patient's cerebrospinal fluid; In a large-scale placebo-controlled trial to test the potential benefits of the drug metformin, researchers are pleased that metformin can be used as a potential treatment for C9-ALS/FTD and other repetitive dilating disorders, as by lowering LEVELs of RAN protein, metformin may be able to solve some of the most common basic problems in many diseasesRelated: 1 Diabetes drug metformin show promise in mouse study for a common type of ALS 2 tao Zu, Shu Guo, Olgert Bardhi, et alMetformin bards ran through PKR and pathways disease in C9orf722 ALS/FT 2020 Jul 20; 20205748.doi: 10.1073/pnas.2005748117 !--/ewebeditor:.!--webeditor: page title"--3 Tao Zu, BrianGibbens, Noelle SDoty, et alNon-ATG-pre-promoted translation directed by microsatellite expansions, PNAS Jan 4, 2011 108 (1) 260-265; doi: 10.1073/pnas.101343108 (4) Mariely DeJesus-Hernandez, Ian RMackenzie, Bradley FBoeve, et al Expanded GGGGGCC Hexanucleo Nucleo Cause Seventyin in Non-Non coding Region of C9ORF7222 j.neuron.2011.09.011 5 Alan E Renton, Elisa Majounie, Adrian Waite, et al A Hexanucleotide Repeat Expansion expansion in C9ORF72 Is The Cause of 9p21-Linked ALS-FTD, Neuron (2011) doi: 10.1016/j.neuron.2011.09.010 Robert H Brown, D.Phil., M.D., and Ammar Al-Chalabi, Ph.D., F.R.C.P., Dip.Stat Amyotrophic Lateral Sclerosis, N Engl J Med 2017; 377:162-172 doi: 10.1056/NEJMra1603471 !--/ewebeditor.