A new discovery shows how the body normally cleanses the brain of harmful substances associated with Alzheimer’s disease.
In the study, researchers determined that a molecular chaperone, HspB1, works like a waste management company to collect and detoxify high levels of toxic amyloid beta peptide found in Alzheimer’s disease.
Scientists had known that HspB1 was present in the hallmark plaques that build up between the neurons 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 Anil G. Cashikar, Ph.D., the 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.”
Improving our knowledge of the protective mechanism and treatment potential of HspB1 is encouraging, although much work remains to be done, said Cashikar.
Earlier this year, a paper Cashikar published in the journal 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,” he said.
Cashikar believes this natural system can be mimicked by developing a smaller version of the molecular chaperone that could be put into the bloodstream to remove excess Abeta from the brain.
The brain has a natural protective mechanism that likely would prevent its direct application. However, the natural affinity of amyloid beta and HspB1 indicates a more remote approach could be effective.
“We want to come up with smaller versions of HspB1 that can be put into the bloodstream so you can sop up the material from the brain into the blood where it can be cleared more efficiently,” he said.
Cashikar believes he may be able to discover a way to increase brain cells’ natural production of protective HspB1 – a finding that could go a long way toward combating the development or spread of Alzheimer’s disease.