Neuron in situ regeneration promises to treat Parkinson's disease

has been studying molecular biology for more than 40 years, and Fu has never been as excited as he is today - starting with a scientific issue entirely based on interest, "crossing the river with a rock" step by step, and finally making a major breakthroughthis scientific breakthrough not only put him into a new field of "neuroscience", but also will become Parkinson's and other neurodegenerative diseases patients "good news.", a professor in the Department of Cell and Molecular Medicine at the University of California, San Diego, and his team for nearly 15 years have pioneered a "simple" and effective new method of effectively transforming astrocytes into functional neurons in the brain by suppressing a RNA binding protein called PTB, which provides a powerful and viable clinical approach to the treatment of neurodegenerative diseasesThe findings were published on June 25 as a cover article in the journal Naturethe "night before" of scientific breakthrough: the key factor PTB
this is the "ten years of grinding a sword" of the east team of the scientific breakthrougheverything from the important part of the story: an RNA binding protein called PTBXue Willingchao, a researcher at the Institute of Biophysics of the Chinese Academy of Sciencesand one of the authors of the paper, told the China Science Daily :P TB is a variable shear inhibitor, which regulates RNA stability, positioning, selective RNA shearing and so on2009, Fu Xiangdong and then-Bosheng Xuexuan super use of the new technology CLIP-seq, in the genome level to understand the variable splicing regulatory protein PTB, and research confirmed that PTB is a universalexpression of important RNA binding protein, it is linked to a wide range of regulatory network, in neurodevelopment andtumoroccurrence has important functionsFu Xiangdong told China Science Daily that during the study, they also found an important feature of the PTB protein, which has a high expression in all cells but is not expressed in differentiated cells such as nerve cellsIn addition, the expression of PTB protein is high to low during the neurodevelopmental processThe ptB protein is lowered at the same time will induce the expression of another shear regulator nPTB, which is homologous with PTBHowever, since nPTB is difficult to capture in mature neurons, an effective way is to usesiRNAtechnology to knock down the PTB, thereby inducing the rise of nPTB, but this process needs to be repeated, boring and inefficientthen, Xue was more than exploring a "effort-saving" approach: using shRNA technology to create a stable cell line that can knock down PTB for a long timeBut at the same time, it has a "side effect" - cells grow too slowly, even after a few days, when they stop growingthey can't figure it out, so they have to let the cells "self-destruct" in the petri dishA few weeks later, however, a more unexpected "weird" phenomenon emerged: the original "smooth" cells in the petri dish produced a lot of "branches and forks" that looked like extremely nerve cellsintuition tells Pay East that this could be an important scientific discoveryThey then immediately tried different kinds of cells, and found that simply suppressing the PTB protein could turn a variety of differentiated cells, including fibroblasts, into neuronal-like cells and even functional neurons", in fact, we were surprised to produce neurons efficiently in such a simple way"Pay East and Xue Willing Chao are very pleasantly surprisedthe findings have been published in the journal Molecular Cells and Cell, respectively, and are considered important new scientific discoveriesat this point, as they are engaged in molecular biology, they have not thought of applications in the field of neuroscience at alldo "subtraction" of regenerative neurons in situ
studies have shown that the loss or death of a large number of specific neurons in the brain is an important cause of neurodegenerative diseasesIn recent years, it has been widely believed thatregenerative medicine has great hopes for treating these diseases, which are characterized by cell loss Xue wants to tell China Science Daily that people have been working to achieve embryonic stem cells replace loss neurons, but its existence differentiation efficiency is not high, unlimited proliferation leads to tumor and other problems , based on the plasticity of somatic cells, it would be significant to change these cells in situ to directly differentiate them into lost cells However, few studies have shown that transdifferentiated cells can replace lost neurons and reconstruct endogenous neural circuits as mentioned earlier, the Fu-Dong team has demonstrated that in in vitro experiments, many different types of cells can be differentiated into neurons by artificially manipulating PTB levels in cells They further pondered: Is this the same in the body? At the same time, can damaged neuronal circuits be rebuilt? 2013, Qian Hao, a ph.d.i.d., who graduated from the Institute of Biophysics of the Chinese Academy of Sciences, joined Fu Xiangdong as a postdoctoral fellow, and he was trained in systematic neuroscience to inject new strength into the research team they used the brain's richest, malleable non-neuronal cell "stargliated glial cells" as transpolarobjects, and using Parkinson's disease (the cause of Parkinson's disease is the loss of mid-brain black dopamine neurons) as a disease model Fu xiangdong said that the star-shaped glial cells are characterized by when the brain is damaged by nerves, the star glial cells will continue to grow, and then form a glial "scar" to continue to cause nerve damage "If we turn a portion of the growing cells into neurons, that is, we don't scarr and add lost neurons, and we achieve the goal of 'one arrow and two carvings.'" they designed a systematic and rigorous protocol that first injected mice with a toxic dopamine analogue 6-OHDA to "kill" dopamine neurons, causing them parkinson's symptoms such as motor disorders Subsequently, RNA interfering molecules or antisense oligonucleotides (ASOs) expressed by adenoviruses temporarily inhibit the synthesis of PTB and stimulate astrocytes into neurons to "treat" mice experiments showed that some of the astrocytes in the brain in mice were converted into dopamine neurons and matured, and the conversion was efficient, increasing the number by 30%-35% What's more, damaged neural pathways have recovered from the body movements and reactions of the mice, the treated mice returned to normal within 3 months of a single treatment To understand how long recovery lasted, the researchers set aside a two-year observation period for some treated mice (about 2 years of life cycle in mice), and the results showed that the repaired neurons were "life-long healed" without repetition "s experimental results are indeed amazing, but how do you prove that the new neurons that are converted work directly to restore motor function, rather than the overall effect of it after fixing something else? "Review sedituated by peers and let pay to the east they were inspired later, they used a chemical genetic method to test and verify that a special receptor hM4Di is expressed on new neurons in response to "anaesthetic" (CNO, N-chloroxide) that temporarily deprives the new neurons of the ability to communicate with other neurons, interrupting neural pathways but not damage study found that without "anesthetics", motor function was restored after three months, and after adding "anesthetic", the movement disorder reappeared within 60 minutes, but after the anaesthetic effect disappeared, the motor function resumed " these studies provide strong evidence that new neurons that are indeed the result of astrocytes are at work Fu said to the east new strategy brings new hope
reviewers say the study is "revolutionary" "This new strategy for treating neurodegenerative diseases gives us hope that even those in patients who are in the advanced stages of the disease may be able to get help," said William Mobley, a leading neuroscience professor at the University of California, San Diego, who co-authored the study "
talk about the long course of research, Pay to the east has a deep feeling There is a lot of unpredictability in truly original scientific research, he says, and the work is basically "step by step, two or three steps forward at most", while exchanges from different fields, peer advice and even criticism give them a lot of inspiration, "we see all the reviews as motivation to move forward to improve our research." "
to pay east, the study is not over " we offer a whole new way of thinking as a treatment for the disease But the human brain is much more complex than the mouse, and a series of problems, such as whether neurons in the human brain grow, whether they can reconstruct damaged neural pathways, and whether they have side effects, need to be solved slowly "Fu Xiangdong looks forward to this approach in the near future through primate trials, clinical trials , and truly become a treatment for many neurodegenerative diseases such as Parkinson's." (
Bio valley Bioon.com)