In-place regeneration of neurons is expected to treat Parkinson's disease

more than 40 years of molecular biology research, Fu has never been more excited than he is today - from a science issue based entirely on interest, step by step "touching a stone across the river", and finally made a major breakthrough.
breakthrough will not only take him into a whole new field of "neuroscience", but will also be a "good news" for people with neurodegenerative diseases such as Parkinson's.
, a professor in the Department of Cell and Molecular Medicine at the University of California, San Diego, and his team spent nearly 15 years working with them to create a "simple" and effective new method of efficiently transforming astrological glial cells in the brain into functional neurons and reconstructing damaged neural circuits by inhibiting an RNA binding protein called PTB, which provides a powerful clinically viable way to treat neurodegenerative diseases. The findings were published June 25 as a cover article in the journal Nature.this is a scientific breakthrough for the East Team's "Ten Years of Grinding a Sword".
everything, starting with the important role in the story: an RNA binding protein called PTB.Xue Xiaochao, a researcher at the Institute of Biophysics and one of the authors of the paper, told China Science :P TB is a variable-shearing inhibitor that regulates RNA stability, positioning, selective RNA shearing, and so on.
In 2009, Fu Dong and then-Bosheng Xue willing to use the new technology CLIP-seq, at the genomic level to understand the variable shear regulatory protein PTB, and the study confirmed that PTB is a commonly expressed important RNA binding protein, which is linked to a broad regulatory network, in neurodevelopment and tumor occurrence has important functions.
study, they also found an important feature of the PTB protein, which is highly expressed in all cells but not in differentiated cells such as nerve cells,
Fu told China Science. In addition, in the process of neurodevelopment, the expression of PTB protein is from high to low. While the PTB protein is lowered, it induces the expression of nPTB, another shear regulator with PTB, which is ententor.
However, since nPTB is difficult to capture in mature neurons, an effective way is to use siRNA technology to knock down the PTB, thereby inducing the rise of nPTB, but this process needs to be repeated, boring and inefficient.
, Xue explored a "effort-saving" approach: using shRNA technology to build a stable cell line that can knock down PTBs for long periods of time. But it also has "side effects" - cells grow too slowly, and even after a few days, the cells stop growing.
they were puzzled and had to let the cells "self-desitte" in a petri dish. A few weeks later, however, a more unexpected "weird" phenomenon emerged: the otherwise "smooth" cells in the petri dish produced a lot of "branch forks" that looked like nerve cells.
intuition tells Fu to go east, this may be an important scientific discovery. They then immediately experimented with different types of cells and found that simply inhibiting the PTB protein could convert differentiated cells, including fibroblasts, into neuron-like cells and even functional neurons.
" in fact, in such a simple way, the efficient production of neurons, we were surprised. "Pay to the east and Xue wish super is very pleasantly surprised.
, published in the journal Molecular Cells and Cells respectively, are considered important scientific new discoveries.
, but at this point, as they are engaged in molecular biology research, they have not even thought of the application in the field of neuroscience.studies have shown that the loss or death of specific neurons in the brain is an important cause of neurodegenerative diseases. In recent years, it has been widely believed that regenerative medicine has great hope for the treatment of these diseases characterized by cell loss.
Xue told China Science Daily that people have been working hard to replace lost neurons with embryonic stem cells, but their existence is not very efficient differentiation, unlimited proliferation leads to tumor production and other problems.
, based on the plasticity of sophysic cells, it would be significant to change these cells in place so that they directly differentiate into lost cells. However, few studies have shown that differentiated cells can replace lost neurons and reconstruct endologic neural circuits.
As mentioned earlier, the Fudong team has shown that in in-sotrophy experiments, many different types of cells can be transformed into neurons by artificially manipulating PTB levels in cells. They went on to think: Is this the same in the body? At the same time, can damaged neuron circuits be reconstructed?
in 2013, the study's first author, Ph.D. graduate
Biophysics, joined Fu dong team as a postdoctoral student, he was trained in systematic neuroscience, to inject new strength into the research team.
They used the most abundant, malleable non-neuronal cells in the brain, "star-shaped glial cells", as the object of differentiation, and Parkinson's disease (the cause of Parkinson's disease is the loss of mesoplasm dopamine neurons in the central brain) as a model of the disease.
said the characteristics of astrological glial cells are that when the brain is damaged by nerves, asstary glial cells continue to multiplies, and then form glial "scars" that continue to cause nerve damage. "If we turn a portion of the growth cells into neurons, that is, we don't scarr and we can replenish the lost neurons for the purpose of 'one arrow and two carvings'."
they desieded a systematic and rigorous experimental program that first injected mice with the toxic dopamine-liker 6-OHDA to "kill" dopamine neurons, causing them to develop Parkinson's symptoms such as movement disorders. Subsequently, the use of adenovirus-like expression of RNA interference molecules or antonym oligonucleotides (ASOs) temporarily inhibited the synthesis of PTB, and stimulated astrological glial cells into neurons, the mice were "treated."
experiments showed that some astrological glial cells in the brain in mice were converted into dopamine neurons and matured gradually, with high conversion efficiency and an increase in the number of 30%-35%. What's more, damaged neural pathps have also been restored.
the body movements and reactions of the mice, the treated mice returned to normal within 3 months of a single treatment. To see how long recovery lasted, the researchers set aside a two-year observation period for some of the treated mice, which had a life cycle of about two years, and found that the repaired neurons were "lifelong healing" and did not repeat.
" results do work, but how do you prove that the new neurons that are indeed transformed work directly to restore motor function, rather than the overall effect it does when it fixes something else? "They were inspired by peer reviews and suggestions to pay eastwards.
Then they used a chemical genetic method to test and verify that a special subject, hM4Di, was expressed on new neurons in response to "anaesthetic" (CNO, N-chlorine oxide), allowing new neurons to temporarily lose the ability to communicate with other neurons, interrupting neural pathfectes, but the neurons were not damaged.
study found that without "anaesthetic", motor function was restored after 3 months, and after the addition of "anaesthetic", movement disorders re-emerged within 60 minutes, but after a period of time the anesthesia effect disappeared, motor function resumed.
" study data provide strong evidence that new neurons that are indeed formed by the differentiation of astrological glial cells are at work. Fu said to the east. reviewers believe that the study has "revolutionary" significance.
"This new strategy for treating neurodegenerative lesions gives us hope that even those in the advanced stages of the disease may be able to get help," said William Mobley, a distinguished professor of neuroscience at the University of California, San Diego and co-lead of the study. "
talked about the long research process, pay to the east deep feeling. There is a lot of unpredictability in truly original scientific research, he says, and the work is basically "one step at a time, two or three steps forward", while exchanges from different fields, peer advice and even criticism give them a lot of inspiration: "We see all the reviews as a driving force to improve our research." "
in the east, the study is not over.
"We offer a whole new way of thinking about treating diseases. But the human brain is much more complex than mice, in the human brain neurons can be long, whether the reconstruction of damaged neural path, whether there are side effects and a series of problems, still need to be slowly resolved. "Fu is looking forward to this approach in the near future through primate trials, clinical trials, truly become Parkinson's and many other neurodegenerative diseases treatment. (Source: Han Yangmei, China Science Daily)
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