A recent study from UC San Diego has identified a gene, phosphoglycerate dehydrogenase (PHGDH), as a cause of Alzheimer’s disease, revealing its unexpected role in disrupting gene regulation in brain cells. This discovery was aided by artificial intelligence, which helped visualize the three-dimensional structure of PHGDH, leading to insights about its function beyond its known enzymatic role. The study found that higher levels of PHGDH expression correlate with more advanced stages of Alzheimer’s, while lower levels are associated with reduced disease progression. Researchers also identified a small molecule inhibitor, NCT-503, which targets PHGDH’s regulatory function without affecting its enzymatic activity, showing promise in alleviating Alzheimer’s symptoms in mouse models. The findings suggest that intervening in the pathway regulated by PHGDH could prevent the formation of amyloid plaques, a hallmark of the disease. The study highlights the potential for developing new therapeutic candidates aimed at treating spontaneous Alzheimer’s disease. This work marks a significant step toward understanding Alzheimer’s causes and improving treatment options. Future steps include optimizing NCT-503 for clinical trials.
