Washington, Dec 4 (ANI): In a new study, scientists found that dynamic regulation of the chaperone protein Hsp27 is required to get rid of abnormally accumulating tau in the brains of mice genetically modified to develop the memory-choking tau tangles associated with Alzheimer's disease.
The University of South Florida-led study has shown that the effective switching of Hsp27 between its active and deactivated states was critical on two fronts-to promote the recycling of the tau protein in healthy nerve cells and to clear abnormal tau from the brain before the protein could clump together into the sticky tau neurofibrillary tangles that kill brain cells involved in memory formation.
"Our study shows that Hsp 27 may be a double-edged sword depending upon the contextual environment of neurons in the brain," said the study's principal investigator Chad Dickey.
"By better defining the mechanisms linking chaperone proteins to both the tau aggregation and degradation pathways, we can move toward more individualized, effective therapies targeting Alzheimer's and other distinct neurological disorders," said Dickey.
The USF study was done using mice genetically engineered to develop tau protein tangles like those found in the brains of people with Alzheimer's disease.
In one experiment, the researchers injected into the brains of 4-month-old Alzheimer's mice viral particles expressing either dynamic wild-type Hsp27 or genetically altered Hsp27 that was continuously on or activated.
By four months, the Alzheimer's mice have aged enough to have large amounts of tau accumulated but are still able to clear the protein before insoluble toxic tangles take over.
When they harvested the brain tissue of the mice two months later (at 6 months), the researchers discovered that both variants of Hsp27 interacted with tau.
In another experiment, the researchers examined the physiological effects of Hsp27 overexpression in the brain.
The researchers found that overexpression of wild-type Hsp27 succeeded in rescuing the mice from neuron damage. The genetically altered Hsp27 did not.
The researchers concluded that Hsp27 must be able to fluctuate between activated and de-activated states to succeed at clearing abnormal tau, thus preventing the protein from sticking together and building up excessively in the brain.
In addition, Hsp27 can only be effective in helping maintain healthy tau turnover if the chaperone protein interacts with tau while it's still soluble-before tau has developed into solid nerve-killing tangles. The chaperone protein cannot disrupt already formed tau tangles.
The findings were published in the Journal of Neuroscience. (ANI)