Beta amyloid — the protein associated with Alzheimer’s disease — is responsible for clogging several cell-transport motors necessary for cell division.
This blockage leads to the abnormal cell division and defective neurons associated with the disease, according to researchers at the University of South Florida.
The protein may cause neurons to malfunction, leading to the memory loss that accompanies Alzheimer’s progression, said scientists at the USF Health Byrd Alzheimer’s Institute, the Florida Alzheimer’s Disease Research Center, and Indiana University, who conducted the study using human cell cultures and frog egg extracts.
“It’s kind of like throwing sand in the gears of the cell’s transport machinery,” said first author Sergiy Borysov, Ph.D.
“It keeps the wheels from moving, which interferes with the cell division cycle and ultimately leads to the production of degeneration-prone neurons seen in the Alzheimer’s disease brain.”
The findings help further define how interference with cell division could result in a cascade of events that contributes to the development of Alzheimer’s.
“By identifying a brand new and extremely important target of the amyloid protein’s toxicity, we can develop drugs for Alzheimer’s disease that may protect the motors from inhibition and allow the brain to regenerate properly,” said principal investigator Huntington Potter, Ph.D., a professor of molecular medicine who holds the Pfeiffer Endowed Chair for Alzheimer’s Disease Research.
The latest study builds upon previous research by Potter that shows amyloid protein is responsible for damaging the microtubule transport system that moves chromosomes, proteins and other cargo around inside cells. Microtubules segregate newly duplicated chromosomes during cell division. If the duplicated chromosomes don’t separate properly, they can re-organize inside newly created cells in wrong numbers and with an abnormal assortment of genes.
The researchers suggest that the same motors are needed for both neuron function and production. Properly functioning microtubule motors are especially important in nerve cells, in which molecules related to learning and memory must travel over long distances, Potter said.
Identifying which microtubule motors are directly inhibited by the amyloid protein can lead to the development of more effective drugs or therapies for Alzheimer’s disease, he added.
The study is published online in the journal Cell Cycle.
Source: University of South Florida