Engineered protein that cuts Alzheimer's-linked brain deposits opens potential therapeutic avenue
A KAIST-led research team has found that a protein involved in gene regulation can suppress the harmful aggregation of amyloid-beta, a peptide associated with Alzheimer's disease. The approach also reduced the toxicity of protein aggregates that had already formed.
A KAIST-led research team has discovered that a zinc finger protein can suppress the formation of harmful amyloid-beta protein deposits in the brains of Alzheimer's disease patients. Amyloid-beta is a peptide associated with the disease, and its aggregation can damage nerve cells. The treatment also reduced the toxicity of existing amyloid-beta aggregates.
The researchers identified a specific segment of the zinc finger protein, named ZF2–4, that binds directly to regions of amyloid-beta involved in its aggregation. By binding to these regions, ZF2–4 altered the aggregation of amyloid-beta, suppressing the formation of long, entangled toxic fibrils and reducing the toxicity of existing fibrils.
The team also developed a method for delivering the protein to the brain by attaching a short peptide to the protein, creating a brain-penetrant variant. When administered to a mouse model of Alzheimer's disease, this variant reduced amyloid-beta deposits in the cerebral cortex and hippocampus by about 53%, improving recognition memory in the mice.
However, no significant improvements were observed in other memory and learning tests. While these results provide a promising avenue for developing protein-based therapeutics that target amyloid-beta, further studies are needed to evaluate the therapeutic efficacy and long-term safety of this approach before it can be applied to humans.
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