New organelle discovered that could be used to treat Alzheimer’s disease

(ORDO NEWS) — In addition to the many known organelles (components or “organs” of the cell), scientists have just discovered another one.

These are the so-called BAG2 – membraneless granules formed in the cytoplasm in response to a certain stress. Probably, BAG2 can become the basis for a new therapy for neurodegenerative diseases.

In addition to the nuclei, mitochondria, reticulum, and so on discovered dozens or even hundreds of years ago, there are many other organelles in the cell.

As a rule, they are smaller and perform a specific specific job. In a recent article in the journal Nature Communications , scientists from the United States and Brazil described BAG2 (Bcl2-associated athanogene 2), a new type of organelle that does not have a membrane but is well separated from the cytoplasm by inclusions.

In this respect, BAG2 resembles the so-called stress granules and processing bodies (P-bodies), but the new organelles contain neither RNA nor the specialized “mark of death” ubiquitin.

The ubiquitin residue is usually attached to those proteins that the cell then purposefully destroys with the help of proteasomes – molecular machines that perform the work of “garbage disposal”.

“People have known for quite some time that there are several types of membraneless objects floating back and forth in a cell.

However, until recently, it was not known how they maintain their integrity, what they are and why they are needed,” said Kenneth S. Kosik from the University of California at Santa Barbara (USA). Now, thanks to advanced molecular imaging techniques, scientists are finally able to get a good look at these dynamic organelles.

What distinguishes these non-membrane structures from the usual large organelles is the lack of packaging from the lipid bilayer, which also separates the contents of the cell from its environment. Instead, inclusions like BAG2 or P-bodies exist by separating two fluids (their contents and the basic environment of the cell) into phases, much like a drop of oil on the surface of water.

Scientists have found that the newly discovered components of the cell are activated (that is, they pass into a condensed form) under certain stress conditions, including an increase in osmotic pressure.

Stress granules work in much the same way, which, when activated, stop protein synthesis and retain RNA. However, BAG2 takes care of those proteins that have already been synthesized. The fact is that under adverse conditions, they can acquire an incorrect three-dimensional structure and damage cells.

Almost the same thing happens with neurodegenerative disorders. BAG2 not only destroys questionable proteins, but also promotes the work of chaperones – other molecules that help proteins maintain the correct structure.

Despite the absence of ubiquitin, BAG2 still provides targeted destruction of proteins in those same proteasomes. Obviously, for this, the organelle uses some other pathway, in which one of the heat shock proteins (HSP 70) is also involved.

It is especially important that tau protein (MAPT) turned out to be one of the targets of BAG2 , which also easily acquires a pathological form and “sticks together” with its own kind. Tau protein is considered one of the main culprits of Alzheimer’s disease – moreover, it is he who most likely triggers its entire pathogenesis.

In this case, the tau protein ceases to do its job – to hold microtubules (an important component of the cellular skeleton) together, detaches from them and forms pathological inclusions inside neurons. Microtubules, meanwhile, begin to break down, and neurons begin to die.

Therefore, scientists consider the newly discovered organelle a promising target for targeted therapy. By modifying the state of BAG2, namely by controlling its transition to a condensed state, researchers hope to develop new methods for treating diseases associated with a violation of the three-dimensional structure of proteins: Alzheimer’s disease , Parkinson’s disease, and other neurodegenerations.


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