AI hilft dabei, eine Ursache für Alzheimer -Krankheit zu enträtseln und einen therapeutischen Kandidaten zu identifizieren, ein Molekül, das eine spezifische Genexpression blockierte. Bei zwei Mausmodellen der Alzheimer -Krankheit linderte es das Fortschreiten von Alzheimer signifikant mit erheblichen Verbesserungen in Erinnerung und Angst.

AI Helps Unravel a Cause of Alzheimer’s Disease and Identify a Therapeutic Candidate

A new study found that a gene recently recognized as a biomarker for Alzheimer’s disease is actually a cause of it, due to its previously unknown secondary function. Researchers at the University of California San Diego used artificial intelligence to help both unravel this mystery of Alzheimer’s disease and discover a potential treatment that obstructs the gene’s moonlighting role.

The research team published their results on April 23 in the journal Cell.

In further support of that finding, the researchers determined—with the help of AI—that PHGDH plays a previously undiscovered role: it triggers a pathway that disrupts how cells in the brain turn genes on and off. And such a disturbance can cause issues, like the development of Alzheimer’s disease.

With AI, they could visualize the three-dimensional structure of the PHGDH protein. Within that structure, they discovered that the protein has a substructure that is very similar to a known DNA-binding domain in a class of known transcription factors. The similarity is solely in the structure and not in the protein sequence.>

Zhong said, “It really demanded modern AI to formulate the three-dimensional structure very precisely to make this discovery.”

Given that PHGDH is such an important enzyme, there are past studies on its possible inhibitors. One small molecule, known as NCT-503, stood out to the researchers because it is not quite effective at impeding PHGDH’s enzymatic activity (the production of serine), which they did not want to change. NCT-503 is also able to penetrate the blood-brain-barrier, which is a desirable characteristic.

They turned to AI again for three-dimensional visualization and modeling. They found that NCT-503 can access that DNA-binding substructure of PHGDH, thanks to a binding pocket. With more testing, they saw that NCT-503 does indeed inhibit PHGDH’s regulatory role.

When the researchers tested NCT-503 in two mouse models of Alzheimer’s disease, they saw that it significantly alleviated Alzheimer’s progression. The treated mice demonstrated substantial improvement in their memory and anxiety tests. These tests were chosen because Alzheimer’s patients suffer from cognitive decline and increased anxiety.