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Small Molecules Convert Supporting Cells in Damaged Brain Tissue into New Neurons


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Posted 12 February 2019 - 11:22 AM


Researchers here present an interesting approach to regeneration of the brain. Rather than spur greater creation of new neurons, or delivering neurons via cell therapy, they find a way to persuade supporting cells near damaged areas to convert themselves into neurons. They have not yet demonstrated that this will work in animals to restore lost function. In situ cell reprogramming is a part of the field that has a lot of promise, but much of the experimentation has yet to be accomplished. "Reprogramming" covers a wide range of possible goals, from minor changes to encourage cells into greater activity or altered behavior within their type, to the more radical adjustments such as change of type or inducement of pluripotency. It remains to be seen which of these approaches will turn out to be viable in the near term of the next decade or so.

A simple drug cocktail that converts cells neighboring damaged neurons into functional new neurons could potentially be used to treat stroke, Alzheimer's disease, and brain injuries. A team of researchers identified a set of four, or even three, molecules that could convert glial cells - which normally provide support and insulation for neurons - into new neurons. The team previously published research describing a sequence of nine small molecules that could directly convert human glial cells into neurons, but the large number of molecules and the specific sequence required for reprogramming the glial cells complicated the transition to a clinical treatment.

In the current study, the team tested various numbers and combinations of molecules to identify a streamlined approach to the reprogramming of astrocytes, a type of glial cells, into neurons. By using four molecules that modulate four critical signaling pathways, they could efficiently turn human astrocytes - as many as 70 percent - into functional neurons. The resulting chemically converted neurons can survive more than seven months in a culture dish in the lab. They form robust neural networks and send chemical and electrical signals to each other, as normal neurons do inside the brain.

The researchers had previously developed a gene therapy technology to convert astrocytes into functional neurons, but due to the excessive cost of gene therapy - which can cost a patient half a million dollars or more - the team has been pursuing more economical approaches to convert glial cells into neurons. The delivery system for gene therapies is also more complex, requiring the injection of viral particles into the human body, whereas the small molecules in the new method can be chemically synthesized and packaged into a pill.

Link: http://science.psu.e...news/Chen2-2019


View the full article at FightAging




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