Introducing the brain: synapse population controls (Introduction)

by David Turell , Monday, July 20, 2020, 20:43 (1585 days ago) @ David Turell

Proteins found that protect synapses from removal:

https://www.sciencedaily.com/releases/2020/07/200717133234.htm

"Researchers at The University of Texas Health Science Center at San Antonio (UT Health San Antonio) have discovered a new class of proteins that protect synapses from being destroyed.

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"'We are studying an immune system pathway in the brain that is responsible for eliminating excess synapses; this is called the complement system," said Gek-Ming Sia, PhD, assistant professor of pharmacology in UT Health San Antonio's Long School of Medicine and senior author of the research.

"'Complement system proteins are deposited onto synapses," Dr. Sia explained. "They act as signals that invite immune cells called macrophages to come and eat excess synapses during development. We discovered proteins that inhibit this function and essentially act as 'don't eat me' signals to protect synapses from elimination."

"During development, synapses are overproduced. Humans have the most synapses at the ages of 12 to 16, and from then to about age 20, there is net synapse elimination that is a normal part of the brain's maturation. This process requires the complement system.

"In adults, synapse numbers are stable, as synapse elimination and formation balance out. But in certain neurological diseases, the brain somehow is injured and begins to overproduce complement proteins, which leads to excessive synapse loss.

"'This occurs most notably in Alzheimer's disease," Dr. Sia said.

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"'We've known about the complement proteins, but there was no data to show that there were actually any complement inhibitors in the brain," Dr. Sia said. "We discovered for the first time that there are, that they affect complement activation in the brain, and that they protect synapses against complement activation."

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"The researchers focused on a neuronal complement inhibitor called SRPX2. The studies are being conducted in mice that lack the SRPX2 gene, that demonstrate complement system overactivation and that exhibit excessive synapse loss."

Comment: As with feedback loops for controls, there are also counterbalancing systems for positive or negative actions. And as being discussed there are mistakes in rapidly moving molecular actions.