Posts tagged antioxidants
Articles and news from the latest research reports.
A proposed link between aging, autism, and oxidation
Like any factory, the body burns oxygen to get energy for its various needs. As a result, detrimental byproducts are released and our cells try to clean up shop with antioxidants. But as we age, this process becomes a losing battle.
“Oxidation inexorably moves us along toward an oxidized state,” said pharmaceutical sciences professor Richard Deth. “You have to deal with it progressively.”
One option is to slow down the synthesis of new proteins, a process that requires energy. Indeed, as we age, we produce fewer new proteins, which explains why our capacity for learning and healing suffer as we grow old.
Since every protein originates from instructions in the DNA, protein synthesis can be slowed down by turning off particular genes. A process called epigenetic regulation accomplishes the task by adding molecular tags on top of the genome. The protein methionine synthase regulates this process. But what regulates methionine synthase? Oxidation.
“This enzyme is the most easily oxidized molecule in the body,” said Deth, whose research on the subject was recently published in the journal PLOS ONE. The senior author for the study, Christina Muratore, received her doctorate in pharmaceutical sciences from Northeastern in 2010.
Whenever the body is under oxidative stress, Deth explained, methionine synthase, or MS, stops working. He and his team hypothesized that MS plays an important regulatory role in aging and that it might be impaired in autism, which Deth has connected to unchecked oxidative stress in previous research.
To examine their hypothesis, the researchers looked at postmortem human brain samples across the lifespan, with subjects as young as 28 weeks of fetal development to as old as 84 years. They measured the levels of a molecule called MS mRNA, which transcribes the genetic code for methionine synthase into actual protein.
As the subjects aged, their brain tissue showed lower levels of MS mRNA. But, surprisingly, the levels of the protein itself remained constant across the lifespan.
Deth and his colleagues suspect that this observed decrease in MS mRNA over our lives may act as a check in the system to save energy that we no longer have in plentiful supply and to slow down oxidative stress. “One way that the system can guard against too much protein synthesis is to restrict the amount of mRNA,” Deth said.
The team also compared MS protein and mRNA levels between brain tissue samples from autistic and normally developing subjects. Autistic brains had markedly less MS mRNA than the control samples but similar protein levels. Additionally, the age-dependent trend seen in normally developing brains was not mimicked among the autistic sample.
If decreased MS mRNA does mean decreased protein production, it’s no big deal for adults who don’t need to make new proteins as often. But for the developing brain, new proteins are critical. “Your capacity for learning might be prematurely reduced because metabolically you can’t afford it,” Deth suggested.
While the results are preliminary and will benefit from repeated studies and more investigation, Deth’s findings add to a growing body of evidence linking both aging and autism to oxidative stress.
Powerful class of antioxidants may be potent Parkinson’s treatment
JUL 23, 2012
A new and powerful class of antioxidants could one day be a potent treatment for Parkinson’s disease, researchers report.
Dr. Bobby Thomas
A class of antioxidants called synthetic triterpenoids blocked development of Parkinson’s in an animal model that develops the disease in a handful of days, said Dr. Bobby Thomas, neuroscientist at the Medical College of Georgia at Georgia Health Sciences University and corresponding author of the study in the journal Antioxidants & Redox Signaling.
Thomas and his colleagues were able to block the death of dopamine-producing brain cells that occurs in Parkinson’s by using the drugs to bolster Nrf2, a natural antioxidant and inflammation fighter.
Stressors from head trauma to insecticide exposure to simple aging increase oxidative stress and the body responds with inflammation, part of its natural repair process. “This creates an environment in your brain that is not conducive for normal function,” Thomas said. “You can see the signs of oxidative damage in the brain long before the neurons actually degenerate in Parkinson’s.”
Nrf2, the master regulator of oxidative stress and inflammation, is – inexplicably – significantly decreased early in Parkinson’s. In fact, Nrf2 activity declines normally with age.
“In Parkinson’s patients you can clearly see a significant overload of oxidative stress, which is why we chose this target,” Thomas said. “We used drugs to selectively activate Nrf2.”
They parsed a number of antioxidants already under study for a wide range of diseases from kidney failure to heart disease and diabetes, and found triterpenoids the most effective on Nrf2. Co-author Dr. Michael Sporn, Professor of Pharmacology, Toxicology and Medicine at Dartmouth Medical School, chemically modified the agents so they could permeate the protective blood-brain barrier.
Both in human neuroblastoma and mouse brain cells they were able to document an increase in Nrf2 in response to the synthetic triterpenoids. Human dopaminergic cells are not available for research so the scientists used the human neuroblastoma cells, which are actually cancer cells that have some properties similar to neurons.
Their preliminary evidence indicates the synthetic triterpenoids also increase Nrf2 activity in astrocytes, a brain cell type which nourishes neurons and hauls off some of their garbage. The drugs didn’t protect brain cells in an animal where the Nrf2 gene was deleted, more proof that that Nrf2 is the drugs’ target.
The researchers used the powerful neurotoxin MPTP to mimic Parkinson’s-like brain cell damage in a matter of days. They are now looking at the impact of synthetic triterpenoids in an animal model genetically programmed to acquire the disease more slowly, as humans do. Collaborators at Johns Hopkins School of Medicine also will be providing induced pluripotent stem cells, adult stem cells that can be coaxed into forming dopaminergic neurons, for additional drug testing.
Other collaborators include scientists at Weill Medical College of Cornell University, Johns Hopkins School of Public Health, Moscow State University, Tohoku University and the University of Pittsburgh.
Source: EarthSky