A research team led by Professor Mi Hee Lim at KAIST, the Korea Advanced Institute of Science and Technology, reports that a protein fragment cut amyloid-beta deposits by about 53 percent in a transgenic mouse model of Alzheimer's disease. The fragment, a segment of a zinc finger protein called ZF2-4, was fitted with a short peptide called P9 to help it cross the blood-brain barrier.
The work was published online in Advanced Science on 30 September (DOI 10.1002/advs.77886) and announced by KAIST in early November. The team included researchers from Jeonbuk National University, KRIBB, KBSI and the Institute for Basic Science.
A gene regulator put to a new use
Zinc finger proteins are best known for regulating genes. Using computer simulations and experiments, the team found that the ZF2-4 segment binds directly to regions of amyloid-beta that drive its aggregation, the clumping that produces the plaques seen in Alzheimer's disease.
In laboratory tests the segment suppressed the formation of new amyloid-beta fibrils. It also acted on fibrils that had already formed, breaking them into short fragments that were less toxic to cells.
Getting it into the brain
The blood-brain barrier restricts what can enter the brain, which makes it hard to deliver protein therapies. The team attached P9, a short peptide that helps molecules cross the barrier, to ZF2-4 to create ZF2-4-P9. The peptide is the delivery shuttle here. The protein segment is what acts on amyloid-beta.
What the mouse study showed
In the transgenic Alzheimer's mice, ZF2-4-P9 reduced amyloid-beta deposits by about 53 percent in both the cerebral cortex and the hippocampus compared with controls. Microglial activation, a sign of brain inflammation, fell by about 29 percent in the cortex and about 50 percent in the hippocampus.
Recognition memory improved. Other learning and memory tests showed no significant improvement.
What is still unknown
The release and coverage do not give the P9 sequence or the dose, route and schedule used in the mice. Efficacy in people and long-term safety have not been established, and the study does not say whether the approach could be made into a medicine.
OrientSciences worked from the KAIST release and news coverage of it and did not read the full paper.