AUGUSTA, Ga. Scientists have shown a molecular chaperone is working like a waste management company to collect and detoxify high levels of toxic amyloid beta peptide found in Alzheimer's disease.
It was known that the molecular chaperone, HspB1, was present in the hallmark plaque of Alzheimer's patients but its role remained a mystery.
"What we have found is HspB1 is a protective mechanism that tries to get rid of the toxic oligomers or aggregates of amyloid beta that occur in Alzheimer's," said Dr. Anil G. Cashikar, Biochemist at Georgia Health Sciences University's Center for Molecular Chaperones and Radiobiology. He is corresponding author of the study published in Molecular and Cellular Biology.
Amyloid beta peptide, or Abeta, is believed to start the cascade of events that leads to brain cell damage and death in Alzheimer's: as levels increase, the peptide starts clumping in the brain. In fact, high levels in the spinal fluid are a diagnostic marker for the disease. Molecular chaperones are known for their propensity to respond to disease-producing misfolded proteins, which is how the body views excessive Abeta.
While resulting plaques occupy prime real estate in the brain, it's still better than toxic Abeta killing neurons, Cashikar said. "We think maybe the system gets overwhelmed."
Acknowledging much work remains, the scientist is excited about identifying the protective mechanism and exploring its treatment potential.
Earlier this year, a paper Cashikar published in PLoS One showed deleting genes with a similar function from a mouse model of Alzheimer's worsened disease symptoms. The new study also showed neurons from HspB1-deficient mice were more sensitive to the toxic ravages of Abeta.
"HspB1 is present because its function is to protect cells. The implication is if we can elevate the levels of this molecular chaperone, we may be able to handle the situation a little better," Cashikar said.
|Contact: Toni Baker|
Georgia Health Sciences University