Scientists Restore Memory in Alzheimer's Mice by Blocking a Single Protein

Scientists Restore Memory in Alzheimer’s Mice by Blocking a Single Protein

A research team at Cold Spring Harbor Laboratory has achieved a significant breakthrough in Alzheimer’s disease treatment. They found that blocking a protein called PTP1B can improve learning and memory in a mouse model of Alzheimer’s disease, while helping the brain’s immune cells clear harmful amyloid-β (Aβ) plaques.

From Discovery to Breakthrough

The study’s lead investigator, Professor Nicholas Tonks at Cold Spring Harbor Laboratory, first discovered PTP1B in 1988 and has spent decades studying its role in health and disease. In this latest work, Tonks collaborated with graduate student Yuxin Cen and postdoctoral fellow Steven Ribeiro Alves to find that PTP1B interacts with another protein called spleen tyrosine kinase (SYK).

SYK helps control microglia — the brain’s immune cells — which are responsible for clearing Aβ plaques. “Over the course of the disease, these cells become exhausted and less effective,” says Cen. “Our results suggest that PTP1B inhibition can improve microglial function, clearing up Aβ plaques.”

Multi-Faceted Treatment Potential

Alzheimer’s disease is strongly associated with obesity and type 2 diabetes, both of which are recognized risk factors for the condition. Since PTP1B is already considered a therapeutic target for metabolic disorders, this discovery could offer a broader treatment strategy for Alzheimer’s.

Current therapies for Alzheimer’s largely focus on reducing Aβ buildup, but their benefits are often limited for many patients. “Using PTP1B inhibitors that target multiple aspects of the pathology, including Aβ clearance, might provide an additional impact,” says Ribeiro Alves.

Moving Toward the Clinic

The Tonks lab is now collaborating with DepYmed, Inc. to develop PTP1B inhibitors for several medical applications. For Alzheimer’s disease, Tonks envisions combining these inhibitors with existing approved drugs. “The goal is to slow Alzheimer’s progression and improve quality of life of the patients,” he said.

This research opens an important avenue for developing new Alzheimer’s treatments. Given the existing research foundation for PTP1B inhibitors in metabolic diseases, the clinical translation pathway may be smoother than for entirely new therapeutic targets.

Source: ScienceDaily