Scientists say they have uncovered the mechanisms by which an anti-aging gene prevents death of brain cells, findings with critical implications for future treatments of such diseases as Alzheimer's and Parkinson's.
In a report published in the journal Science, the researchers from the University of California, Los Angeles, said the gene BCL-2 thwarts the entire cycle of neuron damage, degeneration and death."The study is important because it sheds light on the pathology of degenerative neurological diseases that often accompany aging and suggests a possible therapeutic approach," said head researcher Dr. Dale Bredesen.
The scientists found BCL-2 decreases brain cells' production of reactive oxidants, free radical molecules derived from oxygen but with an unpaired electron that pose a lethal threat to cells.
"The exciting thing about this finding is that BCL-2 prevents cell death from conditions that are analogous to Alzheimer's, Parkinson's and other degenerative diseases," Bredesen said.
"In addition, we now understand for the first time how BCL-2's protective influence works."
The study has key implications for future therapies, from gene manipulation to replace BCL-2 in brain cells to increasing anti-oxidant levels in other, simpler ways, the researchers said.
"At least now we know where to focus our efforts," Bredesen said.
The UCLA team previously had found the gene protects neurons from death, but until now the specific mechanisms were not understood.
The new study showed BCL-2 prevents cell death by decreasing the cells' production of so-called "reactive oxygen species," Bredesen said.
"Typically, 1 to 5 percent of oxygen molecules utilized by cells become super-oxides - a type of free radical - which are responsible for aging and which have been linked to many degenerative neurological diseases," he said.
The study also for the first time conclusively links apoptosis - programmed cell death - with aging.
And it proves the source of the cell damage that eventually causes apoptosis, the researchers said.
"These cells `blow out' like worn tires," Bredesen said. "What we've found is that the cell membrane becomes damaged by a process called lipid peroxidation. This happens when hydrogen peroxide, produced by the oxygen-based free radicals, weakens the membrane and causes it to rupture."
While damage to cells without BCL-2 rises dramatically, those with the gene are fully protected, the scientists found in the study, which was funded by the National Institutes of Health.
"The whole process of cell damage, degeneration and death is now more clear, and BCL-2 prevents the whole cycle," Bredesen said. "We believe it is a very important gene."