Researchers at ETH Zurich have developed an active ingredient that slows typical Alzheimer’s symptoms in mice. The project was led by Ursula Quitterer, professor of molecular pharmacology, and the findings are published in Cell Reports Medicine. The research began almost 20 years ago, after Quitterer received brain tissue samples from surgeries at a hospital in Cairo. The team concentrated on the enzyme GRK2, which helps cells respond to signals and supports nerve cell function.
Quitterer’s group identified two molecular forms of GRK2: a normal, functional protein and an inactivated form produced by metabolism. The inactivated form accumulates in large amounts in the brain tissue of dementia patients and in a mouse model of Alzheimer’s. Molecular analyses and mouse experiments showed that inactive GRK2 aggregates on mitochondria, blocks mitochondrial pores, reduces available cellular energy and raises intracellular stress. The inactive enzyme also promotes production of amyloid beta, which raises stress further and creates a self-perpetuating cycle of aggregation and damage.
To interrupt this cycle, the researchers designed several chemical compounds and tested them in cell cultures and in mice. One compound, called Compound 10, proved especially effective: it prevented GRK2 aggregation, improved mitochondrial function, reduced amyloid beta deposition, and helped nerve cells maintain function and survive longer. Treated mice also showed benefits outside the brain, including improved heart function and signs of slower ageing such as fewer grey hairs. The team has applied for a patent, regards the basic research as complete, and is now seeking a company to develop the compound further. Current medicines do not cure Alzheimer’s and at best delay progression by several months; Compound 10 works via GRK2 and could be combined with other treatments to improve patients’ quality of life.
Difficult words
- active ingredient — substance that produces the main effect in a medicine
- enzyme — protein that speeds up chemical reactions in cells
- aggregate — to form a clump or group togetheraggregates
- mitochondrion — cell parts that produce energy for the cellmitochondria
- amyloid beta — protein fragment that builds up in Alzheimer's brains
- inactivated form — version of a protein that no longer works
- patent — official right to control and sell an invention
- progression — process of a disease getting worse over time
Tip: hover, focus or tap highlighted words in the article to see quick definitions while you read or listen.
Discussion questions
- What are the possible advantages and risks of combining a GRK2-targeting compound with existing Alzheimer’s treatments?
- How might improvements in mitochondrial function affect symptoms of neurodegenerative diseases in general? Give reasons based on the article.
- What challenges do you think researchers face when moving from mouse studies to developing a compound for human patients?
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