Scientists of the Case Western Reserve University School of Medicine have identified theATAD3Aone key protein molecule that plays an important function in the accumulation of cholesterol in the braintriggering the development ofAlzheimer’s (AD).
This discovery is very important at a time when the progression of Alzheimer’s disease is becoming alarming. In fact, it is estimated that, in the United States alone, 11% of individuals over 60 have been diagnosed with AD and the WHO predicts that an increase in Alzheimer’s diagnoses will increase by the millions every year.
AD is an age-related neurodegenerative disease that causes progressive cell death, resulting in memory loss and cognitive dysfunction.
The numbers on the disease are staggering: More than 5.7 million people have AD, and that group is estimated to reach 14 million by 2050, according to the Alzheimer’s Association. That number is projected to rise to 16 million by 2050.
The results of the Research have been published in the scientific journal Nature Communications.
ATAD3A molecule: some details on the study
Xin Qi’s lab, a professor of physiology and biophysics at the School of Medicine, developed and patented a peptide inhibitor previously in hopes of treating AD and Huntington’s disease..
The scientist stated that this study found that mice, when treated with the peptide inhibitor, demonstrated 50% restored memory function, based on tests such as how easy it was to walk mazes.
To better understand the new research, you first need to know what the risk factors lead to Alzheimer’s, such as: cardiovascular diseases; aging; cholesterol in the brain. These factors play a key role in understanding the development of the disease.
Brain cells communicate through cholesterol-rich cell membranes, a process that occurs naturally and is essential for healthy function cerebral. Research shows that the brain contains 23-25% of the cholesterol in the human body.
“Cholesterol builds up in the brain and causes neuron damage – long thought to play a role in Alzheimer’s disease pathology“, Explained Qi:”However, what causes cholesterol to accumulate in the brain remains unknown and may contain answers. “
Research carried out by scholars at Case Western Reserve University School of Medicine is the result of more than five years of research on the role of cholesterol in the brain and its relationship to AD. The researchers set out to address two main questions: What role does cholesterol play in the brain in disease? How can this new pathway be used for future treatment options?
Qi, the senior author of the paper, said the study focused on the protein-coding gene, ATAD3A. Not much is known about how the protein functions within neurodegenerative diseases.
“In Huntington’s disease, the ATAD3A molecule becomes overactive and is oligomerized (repeated), which is a cause of the disease“, Said Qi:”We worked with data scientists to see if ATAD3A also has a link to Alzheimer’s and, to our surprise, we found that the molecule is a leading candidate linked to Alzheimer’s. ”
From this information, the researchers gathered data by analyzing models and found a pathway linking ATAD3A and brain cholesterol.. The researchers found that once ATAD3A is formed by repeating similar or identical parts through a process called oligomerization, it suppresses another protein called CYP46A1.
The new protein then prevents cholesterol from being metabolized in the brain, which means it builds up. Researchers have linked cholesterol buildup in the brain to disease progression in neurodegenerative diseases.
The data show that ATAD3A, especially during oligomerization, could be the cause of AD development. With a possible target identified, Qi has the belief that the next step to treatment lies in the peptide inhibitors, which bind to ATAD3A and block it from acting.
“The models treated with the peptide showed improved performance in memory tests “, Qi specified. “They showed greater memory retention, stronger cognitive activity, and up to 50% restored memory damage“. This means that targeting ATAD3A oligomerization can likely slow the progression of Alzheimer’s disease, further testing is underway. The oligomerization of ATAD3A opens up new avenues for more efficient treatments against Alzheimer’s disease.
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