Researchers at ETH Zurich have uncovered a surprising cellular mechanism that may help explain how Alzheimer's disease progresses. Their work centers on the mitochondria, the cell's energy hubs, and on an enzyme called GRK2.
In the study, an experimental molecule known as Compound 10 (CPD10) reduced Alzheimer's-like changes in mice by preventing a damaged form of GRK2 from forming clusters around mitochondria. When that buildup was blocked, the cells produced energy more efficiently and showed less disease-related stress.
A New Angle on Cellular Stress
Under normal conditions, GRK2 helps cells respond to signals and stress. But the ETH Zurich team found that in Alzheimer's-like conditions, the enzyme can become chemically altered, lose its usual function, and accumulate in harmful clumps. Those clumps were also seen in brain tissue linked to dementia and in mouse models of the disease.
The researchers say this buildup interferes with mitochondrial pores, limiting energy supply and creating a stress cycle inside nerve cells. That cycle appears to encourage the production of amyloid beta, a protein fragment strongly associated with Alzheimer's, which in turn adds more pressure on brain cells.
The study also pointed to TOMM6, a protein involved in moving materials into mitochondria, as part of the same chain of events. When GRK2 aggregated, TOMM6 did as well, further weakening mitochondrial performance.
Compound 10 Shows Promise in Mice
To interrupt this process, the team tested several candidate molecules. CPD10 stood out. In laboratory and animal tests, it reduced GRK2 clumping, supported healthier mitochondria, lowered amyloid beta levels, and helped nerve cells survive longer.
The benefits were not limited to the brain. Mice treated with the compound showed slower nerve-cell loss, better preserved brain connections, improved heart function, and longer lifespans. The treatment also appeared to reduce damage linked to tau, another protein involved in Alzheimer's biology.
The findings do not yet translate into a human therapy, but they offer a fresh target for future drug development. The researchers have filed for a patent and are seeking a partner to advance the compound into further testing.
Published in Cell Reports Medicine, the study adds a new layer to Alzheimer's research and suggests that protecting mitochondrial energy flow could become an important strategy in the years ahead.
