Scientists Discover a New Cause for Alzheimer's Progression with the Help of Artificial Intelligence
Scientists Discover a New Cause for Alzheimer's Progression with the Help of Artificial Intelligence
Using artificial intelligence.. Discovery of a new role for the PHGDH gene in the progression of Alzheimer's disease
A recent scientific study published on April 23, 2025, in the journal Cell, revealed a surprising and fundamental role for the PHGDH gene in the progression of Alzheimer's disease, as it is no longer viewed merely as a biological marker of the disease's presence, but as a direct participant in its mechanisms, through disrupting gene regulation inside the brain.
The research team at the University of California, San Diego used artificial intelligence techniques to analyze complex genetic and cellular data, and discovered that the activity of the PHGDH gene causes regulatory disruptions at the DNA level, which in turn lead to changes in the functions of nerve cells that pave the way for Alzheimer's. This activity is entirely different from its previously known enzymatic role in synthesizing serine (an amino acid important for brain functions).
Alzheimer's.. The Mysterious Disease
Nearly one in every nine people over the age of 65 suffers from Alzheimer's disease, the most common form of dementia. While some cases have been linked to specific genetic mutations, the vast majority of cases remain genetically unexplained, which makes early diagnosis and effective treatment difficult.
The findings of this study represent a shift in scientists' understanding of Alzheimer's, as they open the door to new treatment models that may focus on disrupting the regulatory effects of the PHGDH gene, rather than targeting only its enzymatic activity.
The Importance of Artificial Intelligence in Medical Research
Artificial intelligence plays an increasing role in accelerating medical discoveries, especially in complex diseases such as Alzheimer's, where it helped detect precise genetic patterns that are difficult for humans to trace manually. This study is a clear example of how modern technologies can reshape our understanding of chronic neurological diseases.
The research team, led by Professor Sheng Zhong, a professor at the University of California, San Diego, conducted an in-depth study analyzing the PHGDH gene, revealing precise details about its role in the progression of Alzheimer's disease. The results showed that elevated levels of gene expression of this gene coincide with the advancement of the pathological condition, while lowering its levels in mice led to a reduction in the severity of the disease's symptoms, which is direct evidence that PHGDH is not merely a biomarker, but an actual causal gene that contributes to the onset and progression of Alzheimer's.
What Is Gene Expression?
The term Gene Expression refers to the process of converting the genetic information in a gene (DNA) into a functional product, such as a protein or an enzyme. This process is vital for understanding many diseases, as an increase or decrease in the activity of certain genes can lead to functional disorders, as is the case in cancer and neurological diseases such as Alzheimer's.
Artificial Intelligence Reveals a Hidden Structure
To understand how PHGDH affects the progression of the disease, the team used advanced artificial intelligence tools to model the three-dimensional structure of the gene, only to discover that it has a sub-structure similar to that found in transcription factors – proteins that control the switching on or off of genes inside cells. This discovery was surprising, as it was not previously known that the PHGDH gene had regulatory capabilities over DNA.
A Direct Effect on the Brain
The study indicates that this new regulatory function of the gene directly affects gene networks in the brain, leading to neurological disorders that pave the way for the development of Alzheimer's. This redirects attention toward new therapeutic possibilities that target this structure or reduce its activity in the early stages of the disease.
Statements from the Team Leader
Sheng Zhong said, commenting on the discovery: This level of understanding could not have been reached without the advanced artificial intelligence techniques that helped us model the three-dimensional structure of the gene with high precision. These findings change the way we understand Alzheimer's from the ground up.
The Therapeutic Molecule NCT-503: A Promising New Approach in Combating Alzheimer's
After the researchers identified the causal role of the PHGDH gene in the progression of Alzheimer's disease, their efforts turned toward developing a therapeutic means that targets the source of the genetic disruption, rather than merely attempting to remove beta-amyloid protein buildups, the approach on which most current treatments rely.
The result was the discovery of a promising therapeutic molecule known as NCT-503, which is distinguished by its ability to inhibit the harmful regulatory activity of the PHGDH gene, without interfering with its normal role in producing the amino acid serine, an essential element in brain functions.
Features of the NCT-503 Molecule
Among the most notable characteristics of this therapeutic molecule:
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The ability to cross the blood-brain barrier, which is an obstacle facing many drugs targeting neurological diseases.
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A clear improvement in cognitive and behavioral functions, as experiments on two Alzheimer's mouse models showed that the mice treated with NCT-503 exhibited:
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A significant improvement in memory
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A decrease in levels of anxiety and stress
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New Horizons for Treating Alzheimer's
Professor Sheng Zhong stated:
“We now have a therapeutic molecule that shows very promising results, and it may pave the way for developing an entirely new class of small-molecule-based treatments to target Alzheimer's.”
This new therapeutic approach is distinguished by the possibility of taking these molecules orally, which is a significant advance compared to current treatments that mostly rely on intravenous injection, increasing patient comfort and improving treatment compliance.
The Next Step
According to the research team, the next step consists of improving the pharmacological properties of the NCT-503 molecule, followed by preclinical studies, in preparation for beginning the approval process from the U.S. Food and Drug Administration (FDA), which brings this discovery closer to becoming an actual treatment that changes the lives of millions of Alzheimer's patients around the world.
A Qualitative Leap in Understanding Alzheimer's: From Symptoms to Genetic Roots
This discovery represents a radical shift in the way scientists deal with Alzheimer's. While most previous efforts focused on treating the apparent outcomes of the disease, such as the accumulation of toxic proteins or the loss of nerve cells, this research turned toward the root molecular cause represented by the genetic regulatory disruption resulting from PHGDH.
Precision Medicine Enters the Alzheimer's Arena
Targeting the PHGDH gene is a living example of the concept of “precision medicine,” which focuses on treating the biological causes specific to each patient, instead of applying uniform treatments. This approach may help in:
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Identifying patients who may benefit most from treatment by examining the gene expression levels of PHGDH.
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Preventing disease progression early when an increase in gene expression is detected before symptoms appear.
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Reducing side effects compared to treatments that target broader brain functions.
Why Is This Discovery Different?
Unlike previous theories that viewed Alzheimer's as a disease resulting from "subsequent damage" in the brain, this research proves that the disease may begin from a disruption in the "programming" of the genes themselves, even before any behavioral or cognitive symptoms appear. This supports what is known as:
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The gene-regulation hypothesis in neurological diseases
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And it opens the field to examining other genes that may play similar roles in diseases such as Parkinson's disease and amyotrophic lateral sclerosis (ALS).
A Look to the Future: Are We Facing a Genetic Vaccine for Alzheimer's?
While the matter is still in its early stages, the success of the NCT-503 molecule encourages the development of:
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Preventive drugs given to people genetically predisposed to the disease.
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And perhaps even genetic vaccines in the future, aiming to modify or suppress the causal genes such as PHGDH before the disease process begins.
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