ETH Zurich's Compound 10 slows nerve-cell death in Alzheimer's mice
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An experimental compound developed by Ursula Quitterer's team at ETH Zurich slowed nerve-cell death and extended lifespan in mice with Alzheimer's disease. Compound 10 prevented the enzyme GRK2 from clumping and allowed mitochondria to function better.
Key Facts
- Brain tissue from people with dementia and a mouse model of Alzheimer's contained unusually large amounts of an inactive form of the enzyme GRK2.
- Inactive GRK2 aggregates collected on mitochondria, blocked mitochondrial pores, and increased production of amyloid beta.
- The research began nearly 20 years ago with brain tissue removed during tumor surgery from dementia and non-dementia patients at Ain Shams University Hospital in Cairo.
- Compound 10 has so far been tested only in mice and in cell cultures.
- The findings were published in the journal Cell Reports Medicine.
GRK2 in Dementia
Ursula Quitterer, Professor of Molecular Pharmacology at ETH Zurich, began studying the enzyme GRK2 nearly 20 years ago using brain tissue from patients treated at Ain Shams University Hospital in Cairo. The tissue had been removed during tumor surgery from people with dementia and from non-dementia patients. GRK2 normally helps cells respond to signals, stress and strain, and supports normal nerve-cell function in the brain. Analyzing those samples and conducting mouse experiments, the team found evidence that GRK2 plays an important role in dementia.
Inactive GRK2 Aggregates
GRK2 exists in cells in two forms: a normal functional form and an inactivated form produced by cellular metabolism. Brain tissue from people with dementia and a mouse model of Alzheimer's contained unusually large amounts of the inactive form. Inactive GRK2 clumped together inside brain cells and collected on mitochondria, blocking their pores and reducing energy supply. This aggregation also increased production of amyloid beta, creating a feedback loop that further stressed nerve cells.
Compound 10 in Mice
To interrupt the harmful cycle, Quitterer and her colleagues created several chemical compounds and tested them in cell cultures and mice. Compound 10 prevented GRK2 molecules from forming aggregates, allowing mitochondria to function better. In treated mice, nerve-cell death associated with dementia slowed significantly and the animals lived longer. The findings were published in the journal Cell Reports Medicine.
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ETH Zurich's Compound 10 slows nerve-cell death in Alzheimer's mice
