New compounds target clumping enzyme to protect brain cells in Alzheimer’s models
An enzyme called GRK2 clumps up and damages cellular powerhouses in the brains of mice with Alzheimer's disease. Newly developed chemical compounds that prevent or eliminate these clumps helped preserve memory and slow brain cell death in the animals.
A specific enzyme called GRK2, which is usually found in the fluid of healthy cells, clumps together and damages brain cells in mice with Alzheimer's disease. This clumping was found to contribute to the buildup of harmful proteins, leading to memory loss and cognitive decline. Researchers at ETH Zurich in Switzerland studied whether abnormal regulation of GRK2 played a role in brain damage seen in Alzheimer's disease.
They observed that in mice with Alzheimer's-like symptoms, GRK2 aggregates were concentrated on the mitochondria, which are responsible for generating energy in cells. Similar patterns were found in human brain tissue samples from patients with dementia likely caused by Alzheimer's. The researchers found that the abnormal GRK2 clumps attach to another protein, TOMM6, which normally helps transport materials across the outer membrane of mitochondria.
They developed a compound called CPD10 to stabilize GRK2 and prevent it from clumping. When treated with CPD10, aging Alzheimer's mice showed healthier mitochondria, fewer beta-amyloid plaques, less toxic tau protein, and experienced less brain cell loss compared to untreated mice.
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