Biological complexity: clearing misfolded proteins (Introduction)

by David Turell , Tuesday, February 18, 2020, 20:16 (1526 days ago) @ David Turell

In extracellular fluid a new found clearing mechanism:

https://phys.org/news/2020-02-cells-misfolded-proteins-tissues.html

" A number of diseases are believed to be caused by the gradual buildup of misfolded proteins that can aggregate together and damage neurons and other cells in the body. To help prevent this damage, cells have developed numerous quality control systems that recognize misfolded proteins within the cell and either fold them back into their correct shape or else degrade them before they start to aggregate.

"'However, approximately 11% of human proteins exist outside of the cell, where they are subjected to even more stresses that may cause them to misfold," says Eisuke Itakura, an assistant professor in the Department of Biology at Chiba University in Japan.

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"A protein called Clusterin can bind to misfolded extracellular proteins and prevent them from aggregating. In the new study, Itakura and colleagues discovered that Clusterin can escort misfolded proteins into the cell and deliver them to the cell's garbage-disposal units—the lysosomes—where they can be degraded. The researchers also discovered that, after binding to misfolded proteins, Clusterin enters cells by binding to proteins known as heparan sulfate proteoglycans, which are present on the surface of almost all human cells.

"Itakura and colleagues found that, together, Clusterin and heparan sulfate proteoglycans allow many different cell types to internalize and degrade a wide variety of misfolded extracellular proteins. "We therefore think that this pathway is a general extracellular protein quality control system responsible for the clearance of misfolded proteins from diverse tissues and body fluids," Itakura says.

"Intriguingly, the researchers also found that Clusterin and heparan sulfate proteoglycans can import amyloid β into cells for degradation. Mutations in the gene encoding Clusterin have been linked to an increased risk of developing Alzheimer's disease, and experiments in rats have shown that injecting Clusterin into the brain can prevent amyloid β-induced neurodegeneration. '"

Comment: Miss-folded protein molecules cannot perform the proper functions of a properly folded protein. It is the folding that creates the functional ability. Obviously life cannot continue without this correction process, which must have been present when Life started. Design is required.