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*For medical professionals only
We hope to develop a drug that works in this way to protect women from the high risk of
Alzheimer's disease.
The researchers found a mechanism in brain tissue that could explain why women are more likely to develop Alzheimer's disease
.
The discovery may help develop new drugs
to treat the disease.
Case Western Reserve University, Oct.
4 -- Researchers at Case Western Reserve University (CWRU) have found that women have higher expression of an enzyme in their brains than men, leading to more accumulation of a protein called tau
。 Tau proteins form toxic protein clumps
in brain nerve cells in Alzheimer's patients.
This enzyme, called ubiquitin-specific peptidase 11 (USP11), is related to the X chromosome, meaning it is present in genes on the X chromosome, which is one
of the two sex chromosomes in each cell.
"We are particularly excited about this discovery because it provides the basis for the development of new neuroprotective drugs," said David Kang, Howard T.
Karsner, the Howard T.
Karsner Professor of Pathology at Case Western Reserve University School of Medicine, who is published in Cell ().
Co-senior author of the study in the journal Cell, "This study also provides a framework for identifying other X-related factors that may increase a woman's susceptibility to tau proteinopathy
.
" The
study was published in the journal Cell (latest impact factor: 66.
850) on October 4, 2022, and women with tau protein were about twice as likely to develop Alzheimer's disease as
men.
The mechanism behind this increased vulnerability is unclear, but one possible explanation is that tau protein deposition is significantly higher
in women's brains.
"When a particular tau protein is no longer needed for the function of its nerve cells, it is usually designated for destruction and clearance," Kang says, "and sometimes this clearance process is disrupted, causing tau proteins to accumulate
pathologically within nerve cells.
" This causes nerve cells to be destroyed, leading to tau proteinopathy, most notably Alzheimer's disease
.
The process of eliminating excess tau protein begins with the addition of a chemical tag
called ubiquitin to the tau protein.
The presence of ubiquitin on tau proteins is regulated by a balanced system of enzymes that add or remove ubiquitin tags
.
Because dysfunction of this balancing process can lead to abnormal accumulation of tau protein in Alzheimer's patients, Kang and co-senior author Jung-A Woo, assistant professor at Case Western Reserve University, conducted a study to investigate why this happens
.
Specifically, they looked for an increase in the activity of the enzyme system that controls ubiquitin tag removal, as overactivation on this side of the balance can lead to pathological tau protein accumulation
.
Professor Kang said: "We think that if this can be identified, then it could provide the basis for the development of new drugs that restore the proper balance
of tau protein levels in the brain.
" They found that naturally expressed levels of USP11 in female brains were higher than in men, and that USP11 levels were strongly associated with brain tau protein pathology in women, but not
in men.
The researchers also found that when they genetically eliminated USP11 from a mouse model of brain tau protein pathology, female mice were preferentially protected from tau protein pathology and cognitive impairment
.
Males also resist tau proteinopathy in the brain, but nowhere near as much as females
.
These results suggest that overactivity of the USP11 enzyme in women leads to increased
susceptibility to Alzheimer's tau pathology.
However, the authors caution that animal models may not be able to fully capture the tau protein pathology
seen in humans.
"In terms of effects, the good news is that USP11 is an enzyme that can traditionally be pharmacologically inhibited
," Kang said.
We hope to develop a drug that works in this way to protect women from a high risk
of developing Alzheimer's disease.
" Case Western Reserve University
References, founded in 1826: Yan Yan, Xinming Wang, Dale Chaput, Min-Kyoo Shin, Yeojung Koh, Li Gan, Andrew A.
Pieper, Jung-A.
A.
Woo, and David E.
Kang.
X-linked ubiquitin-specific peptidase 11 increases tauopathy vulnerability in women.
Cell, 2022 DOI: 10.
1016/j.
cell.
2022.
09.
002Source
: Alzheimer's disease
The author of this article: Alzheimer's disease
Responsible editor: 66questionnaire survey
Stroke (commonly known as "stroke") has the characteristics of "four highs" with high morbidity, high disability rate, high mortality rate and high recurrence rate, acute onset, rapid progression and serious consequences, 1 in every 4 people in the world will have a stroke, 1 person will die of stroke every 6 seconds, and 1 person will be disabled due to stroke every 6 seconds, and the patient's family will suffer huge economic losses and physical and mental suffering
.
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, nor does it assume any responsibility
arising from the fact that the content is out of date and the cited information may be inaccurate or incomplete.
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