The molecular chaperone (a molecule that assists in protein folding), may help to reduce levels of a toxic substance that has been found in many individuals with Alzheimer’s. The toxic substance, amyloid beta peptide (Abeta), is used as a marker for Alzheimer’s and is usually taken from spinal fluid. Abeta is so toxic to brain cells that it usually leads to their damage and eventual death.
Abeta accumulates when proteins are not formed correctly and are either prematurely shortened or folded incorrectly. If many of these misfolded Abeta peptides accumulate in the brain, they begin to form plaques. The job of molecular chaperones is to recognize these misfolded proteins and start a chain of events that destroys the incorrect protein.
The molecular chaperon that recognizes Abeta is called HspB1 (heat shock protein B1). Scientists from Georgia Health Sciences University’s Center for Molecular Chaperones and Radiobiology have found that HspB1 protects brain cells and somehow reduces the levels of Abeta present in the brain. The protective mechanisms are still unknown but scientists at Georgia Health Sciences would like to explore the possibilities of using HspB1 or a derivative to remove Abeta from the brain.
One particular scientist, Dr. Cashikar, documented that mice had increased symptoms of Alzheimer’s if they lacked the genes that function similarly to HspB1. The study also described an increased sensitivity to Abeta in neurons from HspB1-deficient mice.
Dr. Cashikar wants to further study the brain system by producing a small version of HspB1 and place this protein into the bloodstream in efforts to rid the brain of the toxic substance. Heat shock proteins like HspB1 have a high attraction for Abeta, and hopefully this attraction will promote more Abeta being picked up by HspB1 and removed from the brain. Once removed from the brain, Abeta can be deposited into the blood stream where it can be more effectively eliminated from the body. Dr. Cashikar is also investigating methods of enhancing the brain’s regular production of HspB1.
Of note, brain cells produce their own supply of Abeta which may be essential to remove synaptic formations. Yet, scientists are unsure why brain cells would produce an excess amount of Abeta, which eventually leads to their death.