Ai Uncovers a New Culprit and Target for Alzheimer's Disease

A major breakthrough from the University of California San Diego has redefined our understanding of spontaneous Alzheimer’s disease. Using advanced AI-driven protein modeling, researchers have identified that PHGDH: a gene once considered just a biomarker, is in fact a causal driver of disease progression.

In this study, scientists revealed that PHGDH has a previously unknown "moonlighting" role: it disrupts gene regulation in the brain via a DNA-binding substructure, independent of its known enzymatic function in serine production. This dysregulation was shown to trigger early-stage Alzheimer's pathology, even in the absence of known genetic mutations.

Crucially, the team also identified a therapeutic candidate: NCT-503, a small molecule capable of targeting the regulatory (not enzymatic) activity of PHGDH. In preclinical mouse models, NCT-503 slowed disease progression and improved outcomes in memory and anxiety tests, two hallmark symptoms of Alzheimer’s.


Source: University of California - San Diego. "AI helps unravel a cause of Alzheimer's disease and identify a therapeutic candidate." ScienceDaily. ScienceDaily, 25 April 2025. <www.sciencedaily.com/releases/2025/04/250425113453.htm>