Researchers at Cold Spring Harbor Laboratory have found that blocking the protein PTP1B improves memory and boosts plaque clearance in mouse models of Alzheimer's disease. The discovery links the protein to brain immune function and metabolic risks like diabetes and obesity. The team aims to develop inhibitors for potential human treatments.
Scientists led by Professor Nicholas Tonks at Cold Spring Harbor Laboratory have identified PTP1B as a promising target for Alzheimer's treatment. In a new study published in the Proceedings of the National Academy of Sciences, blocking PTP1B enhanced learning and memory in mice with Alzheimer's-like conditions. The protein interacts with spleen tyrosine kinase (SYK), which activates microglia—the brain's immune cells—to clear amyloid-β (Aβ) plaques more effectively. Graduate student Yuxin Cen explained, “Over the course of the disease, these cells become exhausted and less effective. Our results suggest that PTP1B inhibition can improve microglial function, clearing up Aβ plaques.” Postdoctoral fellow Steven Ribeiro Alves added that such inhibitors could target multiple disease aspects beyond current therapies focused on Aβ reduction. Tonks, who discovered PTP1B in 1988, drew from personal experience: “It's a slow bereavement. You lose the person piece by piece,” he said of his mother's Alzheimer's. The finding gains added relevance since PTP1B is already a target for obesity and type 2 diabetes, both risk factors for Alzheimer's. The lab is partnering with DepYmed, Inc., to develop PTP1B inhibitors, potentially combinable with existing drugs. Tonks stated, “The goal is to slow Alzheimer's progression and improve quality of life of the patients.”
