Sub-Journal of "Cell": Muscles are quietly protecting the brain!

As people get older and older, human body functions are constantly deteriorating, including the aging of the brain, which is the degenerative disease of nerves.

Initially, the academic community believed that neurodegenerative disease was a disease that only occurred in a part of the brain, but now more and more evidences show that peripheral tissues are also involved.

But when I knew that muscles are also a great contributor to the protection of the brain, I was a little surprised.
It seems that the brain and muscles have always been opposed.
We even use "muscles in the brain" to laugh at the simple mind and well-developed limbs (of course this is a mistake.
Stereotypes).

A recent study published in the journal Cell Metabolism found that under stress conditions, maltose produced by the breakdown of Amyrel amylase released by muscles can act on the brain to prevent the accumulation of misfolded protein aggregates in the brain.

Researchers believe that this signaling pathway helps fight neurodegenerative diseases, such as age-related dementia and Alzheimer's disease.

Many neurodegenerative diseases originate from the accumulation of disease-causing proteins.

In the body, the ubiquitin-proteasome system is the basic way to degrade misfolded proteins and disease-causing proteins.

The proteasome is monitored by a variety of cellular mechanisms and can dynamically adjust its abundance, composition and activity to meet the challenges of complex body homeostasis.

These adjustments come not only from the cell itself, but also from distant tissues, such as the skeletal muscle to the brain that we are going to talk about today.

In fact, skeletal muscle is involved in affecting the neurodegeneration and aging of the brain and retina.
This phenomenon has been observed in previous studies.

Some researchers believe that such systemic effects may come from muscle growth factor secreted by muscles, but the mechanism has not been fully elucidated.

The researchers first used a common method to induce proteasome stress in Drosophila by RNAi targeting, and found that this caused compensatory changes in muscles, specifically the increase in the expression of chaperone proteins and protease/peptidase.
Promotes the degradation of proteasome substrates.

Interestingly, although this effect occurs in the muscles, the researchers found that the proteasome substrates in the head tissue of fruit flies are also reduced, and the accumulation that would have occurred with age is reversed.

So, who is at work? After comparing RNA sequencing data, the researchers found several muscle growth factors that interact with RNAi.
On this basis, the researchers further tested their actual effects through RNAi or overexpression, and finally found the key, starch.
Enzyme Amyrel.

Experimental results show that Amyrel overexpression can reduce the accumulation of age-related proteasome substrates in the head tissue of Drosophila.

Fluorescent protein labeling showed that Amyrel expressed by skeletal muscle also appeared in the circulation and head, but only the head protein steady-state response to Amyrel's regulation, skeletal muscle was not affected.

The researchers analyzed the specific regulated proteins and found that the accumulation of a pathogenic huntingtin aggregate Htt-polyQ120 and another mutant tauV337M that induce neurodegeneration can be offset by the overexpression of Amyrel to some extent.
.

Amyrel overexpression significantly reduces the deposition of pathogenic proteins.
Obviously, Amyrel is a key stress-induced muscle growth factor, which can improve the protein balance in the aging process and has a protective effect on neurodegeneration induced by pathogenic proteins.

In the experiment, Amyrel overexpression indeed also protected the nerve function of Drosophila.

Amyrel is an amylase, and it is its amylase activity that plays a key role.

Researchers have found that treatment with disaccharide maltose produced by Amyrel hydrolyzing polysaccharides and oligosaccharides can also have the same protective effect.
Maltose itself is a chemical chaperone that can stabilize membrane structure and protein folding.
The maltose transporter Slc45 is also the way.
The role of the key. Slc45-2 is highly expressed in the brain, but rarely expressed in skeletal muscle.
This may explain why the protein homeostasis in the brain is balanced, but the skeletal muscle has no response.

The researchers continued to conduct experiments in HEK293 human cells and brain organoids, and also found that maltose treatment can balance protein homeostasis and preserve neuronal activity.

Maltose treatment reversed the changes in gene expression caused by heat shock.
Corresponding author Dr.
Fabio Demontis said in an interview that the stress response caused in muscles not only affects muscles, but also promotes the regulation of proteins in remote tissues such as the brain and retina.
The stress response is actually the protection of tissues during the aging process.

Researchers believe that the regulation of related signals may help fight neurodegenerative diseases.

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 Reference materials: [1]#%20[2] /03/210326152359.
htm The author of this articleDai Siyu