Drowsiness is also a disease, for which two academics won this year's "Scientific Breakthrough Award"

Masashi Yanagisawa (left) and Emmanuel Mignot (right)

September 22, 2022, is not only World Narcolepsy Day, but also the announcement of the winners of the
2023 Science Breakthrough Award.

It was on this day that one of the three groundbreaking awards in the field of life sciences was awarded to Emmanuel Mignot and Masashi Yanagisawa, who discovered the cause of narcolepsy, and received the "Science Breakthrough Award" on this special day, which can be said to be a full affirmation
of their research.

Narcolepsy, a major type of narcolepsy, how did their research find out and be a boon to people with narcolepsy in the world?

The two scholars deserved the Scientific Breakthrough Award
.

According to the official website of the Science Breakthrough Prize, Emmanuel Mignot and Masashi Yanagisawa found that narcolepsy is caused by the loss of a small group of brain cells that release arousal-promoting substances
.

To figure out what this small group of brain cells is and why the Prize for Scientific Breakthrough considers their discovery to be a "game changer," we have to first figure out what narcolepsy is
.

01 "Game changer" and won the Science Breakthrough Award

Alzheimer's disease and Parkinson's disease are both neurodegenerative diseases, and narcolepsy is actually a neurodegenerative disease, but little was known about the disease until Masashi Yanagisawa and Mignott respectively devoted themselves to the study of narcolepsy
.

Their study showed that at the heart of the disease is a class of proteins — orexins, also known as hypothalamic secretin
.

Xu Min, senior researcher of the Center for Excellence in Brain Intelligence of the Chinese Academy of Sciences and chairman of the Physiology and Pharmacology Committee of the Chinese Sleep Research Association, said, "Sleep is a very common behavior in the biological world, which is an important mechanism for
biological regulation.

Narcolepsy is simply a disorder of
sleep.

The incidence of narcolepsy is 1.

Previously, the cause
of narcolepsy was not clear.

Masashi Yanagisawa and Miguenot, who experimented separately in mice, found that narcolepsy was triggered by the immune system attacking cells that produce orexin
.

As introduced on the official website of the "Science Breakthrough Award", the winner of this award was recognized for its game-changing discovery, and Masashi Yanagisawa and Miguenot changed the "rules of the game" of narcolepsy research
.

Speaking of which, let's introduce two scholars
.

02 Craftsman, who has studied sleep all his life

As scholars at the forefront of research in a certain field, many people often have enough to study only one thing in their lives, and this is the case
with Masashi Yanagisawa and Mignot.

Masashi Yanagisawa has been studying the underlying mechanisms of sleep-wake regulation since his graduate studies, and in 1988, as a graduate student at the University of Tsukuba, he discovered endothelin, a hormone that raises blood pressure, a discovery that caught the attention
of professors.

In 1991, he established an independent laboratory
at the University of Texas Southwestern Medical Center, with the support of Nobel laureates Joseph L.
Goldstein and Michael Brown.
Seven years later, he discovered a brain substance called "orexin," ushering in a new era of sleep research
.
Subsequently, he was elected a member
of the National Academy of Sciences in 2003.

To this day, Masashi Yanagisawa has been committed to research
in this field.
In fact, so did
Mignott of Stanford University School of Medicine.

Miguenott completed his PhD in Molecular Pharmacology at the Université Pierre and Marie Curie and has since pursued a career in the subspecialty
of psychiatry.

It was during this time that Miguenott believed that understanding narcolepsy, could lead to a breakthrough understanding of
sleep research.
From 1933 to 2001, he rose from assistant professor of psychiatry and behavioral sciences at Stanford University to professor, and in 2011 he was named director of
the Center for Sleep Science and Medicine.

During his tenure as an assistant professor, starting in 1990, he isolated genes that cause narcolepsy in dogs such as Dobermans
and Labradors.
Ten years later, he discovered that it was a mutation in orexin receptor 2 that led to narcolepsy
in dogs.
He worked in parallel with scholars such as Masashi Yanagisawa, whose research showed that mice lacking in orexin also suffered from narcolepsy
.

03 Coincidentally, dramatic research converges

As mentioned earlier, Masashi Yanagisawa and Miguenot have been working on sleep-wake regulation, and as early as the 1980s, Mignot and his colleagues began interbreeding with narcolepsy dogs to try to find out the genes
associated with the disease.

After 10 years of research, the research team finally identified genes
that encode two membrane receptors in the brain.
As Miguenot puts it, "When I first started doing this, people said it was crazy because the human genome hadn't even been sequenced
yet.
" But in fact, the hard work paid off, and the 10 years I spent were rewarded
.
”

Mignott didn't know what the function of these newly discovered receptors was, let alone which molecules could target them
.

Around the same time, Masashi Yanagisawa and his colleagues were extracting and purifying protein mixtures from animal brains, working to determine specific proteins that target hundreds of receptors from these extracts
.
Coinciding with Mignot, Masashi Yanagisawa's first target was the receptor that Mignott was also studying, and they found that this receptor reacted to two previously unknown peptides — now known as orexin-A and orexin-B
.

Subsequently, by blocking the orexin-producing genes in mice, Yanagisawa and his team observed that these mice, which were supposed to be active at night, periodically fell into intermittent sleep at night, with symptoms similar to narcolepsy
.
To conduct a controlled trial, they injected orexin into the brains of these mice at night and found that they were able to stay awake
.

Overall, these findings reveal not only the membrane receptor associated with narcolepsy, but also the apraxins
that specifically bind to that receptor to maintain wakefulness in mice.

"It's a very dramatic and exciting fusion of two labs from completely different directions," Masashi Yanagisawa said
.

While it's not entirely clear how people with narcolepsy can't produce orexin in their bodies, Mignot's recent research suggests that this could be an autoimmune disease in which the body's immune system may attack
orexin-producing cells by mistaking them for foreign viruses.

The discoveries of Miguenot and Masashi Yanagisawa not only improved the scientific community's understanding of sleep, but also further stimulated the development
of drugs related to the treatment of narcolepsy.
Although no related drugs have been approved so far, many have entered the clinical trial stage
.

Yanagisawa Masashi said, "If all goes well, then within 3 to 4 years, there will be clinically available drug treatment
.
" ”

Resources:

1.
Scientists who discovered cause of narcolepsy win Breakthrough Prize | New Scientist

2.
What's New! The 2023 Science Breakthrough Award was announced, rewarding protein structure prediction, sleep mechanisms, and quantum information.

3.
Masashi Yanagisawa | TSUKUBA OCW | University of Tsukuba

4.
Breakthrough Prize – Winners Of The 2023 Breakthrough Prizes In Life Sciences, Mathematics And Fundamental Physics Announced

5.
Emmanuel Mignot and Masashi Yanagisawa: 2023 Breakthrough Prize Life Sciences - YouTube