Prof. Michael Glickman..
A vital mechanism that causes the accumulation of protein plaques in the brain has been discovered by scientists at Haifa’s Technion-Israel Institute of Technology and may eventually lead to a cure for the fatal dementia.
The team, who called the work a “breakthrough,” published the findings on Monday in the online edition of Nature Chemical Biology.
Dementias affect an estimated 44 million people around the world, with 60 percent to 80% of them caused by Alzheimer’s disease.
More than five million cases of Alzheimer’s have already been diagnosed in the US alone. According to the Alzheimer’s International federation, due to the aging of the population, including in the developing world, this number will increase to some 75 million in 2030 and 135.5 million in 2050. Already 62% of people with dementia live in developing countries, but by 2050 this will rise to 71%.
A cure for the progressively fatal disease has so far proven elusive, but the Haifa discovery could change this, said biology faculty Prof. Michael Glickman, who headed the team.
The researchers’ discovery is centered on UBB+1, a mutation prevalent in Alzheimer’s victims. The mutation impairs a protein called ubiquitin that marks other proteins to be dismantled by the proteasomes, which are protein complexes whose main role is to degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds.
Previously, the prevailing view among scientists was that UBB+1 disrupts the functioning of the proteasome itself. But in her doctoral dissertation under Glickman’s guidance, Dr.
Daria Krutauz found that in the presence of UBB+1, damaged proteins are apprehended on their way to the proteasome and accumulate without reaching their final recycling destination. As a result, they have more opportunity to form the deadly plaque associated with Alzheimer’s disease.
Ubiquitin is a small regulatory protein that has (ubiquitously) been found in almost all tissues (ubiquitously) of eukaryotic organisms (any organism whose cells contain a nucleus and other structures enclosed within membranes).
In 2004, Technion Profs. Avram Hershko and Aaron Ciechanover and Prof.
Irwin Rose of the Fox Chase Cancer Center Fox Chase in Philadelphia were awarded the Nobel Prize in Chemistry for their discovery of ubiquitin.
“Proteins that constitute major building blocks of our body cells continuously pass through quality control,” explained Glickman. “Defective proteins are sent to the proteasome, a molecular machine found in all of our cells that eliminates defective proteins by recycling them back to their building blocks.
But a small number of them slip through this process.
Proteins that evade the proteasome accumulate and may be harmful when they reach a critical mass, which is often the case at an advanced age.”
“Because our findings run contrary to what was previously believed, this discovery opens new venues for intervention in the hope of developing a cure for Alzheimer’s disease,” said Glickman.
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