Novel membraneless organelle could play a role in Alzheimer’s treatment

Researchers in UC Santa Barbara neuroscientist Kenneth S. Kosik’s lab have discovered a novel organelle — a previously unknown cell structure whose function it is to help clean up faulty proteins in times of stress and keep cells functioning in top condition. Optimizing this membraneless organelle, which they call a BAG2 condensate, could lead to treatments for conditions that are the result of misfolded proteins, including Alzheimer’s disease, Parkinson’s disease and other neurodegenerative conditions. Their results are reported in a paper led by project scientist Daniel C. Carrettiero and published in the journal Nature Communications.

“People have known for quite a while that are a few objects floating around in cells that don’t have membranes,” Kosik said. “And it’s never been clear how they’re held together, what they are and what they’re doing until relatively recently.”

Indeed, thanks to advanced imaging techniques, scientists have uncovered structures that were once invisible, revealing cells for the truly complex and sophisticated systems that they are.

Of particular interest are biomolecular condensates, which don’t have the recognizable cell membrane enclosure, but instead, are separated from the surrounding cytoplasm by a difference in density that can be loosely compared to a drop of oil in water. This liquid-liquid phase separation creates a specialized, relatively concentrated environment for certain functions and reactions. For example, a stress granule is a membraneless organelle that appears when the cell is under stress — maybe there’s too much glucose, maybe it’s too hot or cold, maybe the cell is experiencing dehydration — and its job is to sweep up RNA floating around in the cytoplasm, storing those genetic instructions and pausing their translation into proteins.

“If your cell is under stress, you want to shut down making proteins so you can really conserve your energy and get past the stress,” Kosik explained.

But that’s only part of the picture, according to the researchers.

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