Oxidatieschade verantwoordelijk voor de ziektes van Parkinson en Alzheimer.*
In eerdere studies is reeds vastgesteld dat door genetische afwijkingen beschadiging van het proteïne DJ-1 kunnen optreden die bij (erfelijke) Parkinson verantwoordelijk is voor de neurologische degeneratie. In deze studie zijn de niet erfelijke gevallen (90% van het totaal) bekeken. Gebleken is dat door oxidatieschade ontstaan door het ouder worden en versterkt door toxische stoffen uit het milieu zoals pesticiden, het proteïne DJ-1 beschadigd wordt. Ter voorkoming is het dus belangrijk voeding met voldoende antioxidanten te eten, zoals groene thee en groenten en fruit.
Scientists
Discover Possible Link Between Oxidative Stress And Non-hereditary Degenerative
Disease
The
irreversible neurological degeneration associated with Parkinson's and
Alzheimer's diseases may be the consequence of oxidative stress--the imbalance
of antioxidants and pro-oxidants in cells. This imbalance results in an excess
of reactive oxygen species--harmful oxygen-containing molecules that can cause
damage to proteins. In an issue of the Journal of Biological Chemistry,
scientists from the Emory University School of Medicine report that the protein
DJ-1 is oxidatively damaged in non-hereditary (sporadic) Parkinson's disease.
While scientists do not know the function of DJ-1, they have previously
identified abnormalities in DJ-1 that directly cause hereditary (familial)
Parkinson's disease. About 10 percent of Parkinson's disease cases are
hereditary forms caused by either a genetic deletion or mutations that result in
amino acid substitutions, which can dramatically affect protein structure or
function.
The cause of the 90 percent of Parkinson's Disease cases not influenced by
genetics has remained more of a mystery. Lian Li, PhD, is associate professor of
pharmacology at Emory University School of Medicine and lead author of this
study, which was funded by a grant from the National Institutes of Health.
"One popular theory has suggested that these sporadic cases result from
exposure to environmental toxins, such as herbicides or pesticides," she
says. "Previous research has indicated that these toxins lead to oxidative
stress. While oxidative stress does occur naturally as humans age, further
oxidation caused by toxins may overwhelm the body’s antioxidants."
Until now, attempts to link environmental toxins to oxidation and neurological
disorders have been only somewhat successful, in part because scientists have
been unable to identify the molecular target of oxidation. "This theory [that
toxins cause oxidative stress] has been around for a long time," says Dr.
Li. "But what’s been damaged by this oxidative stress?"
Aware of the connection between DJ-1 mutations and familial Parkinson's disease,
Dr. Li and her collaborators examined the oxidation levels of the protein in
sporadic cases. Their hypothesis that DJ-1 was the missing link proved to be
correct: DJ-1 in patients who had Parkinson's disease showed signs of oxidative
damage, including structural changes as the protein accumulated additional
oxygen molecules (carbonylation and methonine oxidation).
These modifications to DJ-1 caused by the oxidative stress are irreversible and
irreparable. Like familial Parkinson's disease, the structural changes to the
DJ-1 protein in sporadic Parkinson's disease signal an abnormality, leading to
the eventual degradation and loss of the protein. "The protein unfolds and
cannot function normally," Dr. Li explains. "Not recognizing the
unfamiliar shape, the protein is broken down by the cell. The end result is the
same: you lose your protein. Any mutation or modification causing this protein
to lose its function will then lead to neurodegeneration in Parkinson's disease."
Now that Dr. Li and her team are clear that a relationship between DJ-1 and
neurodegeneration exists, they are preparing to extend their examination into
the protein's role. Based on biochemical analysis, Dr. Li believes DJ-1 may
serve as a protease, activating and deactivating a protein by cleaving the bonds
that connect its amino acids. Dr. Li is also currently exploring the possibility
that DJ-1 may serve as an antioxidant, and that when mutated or damaged, the
protein cannot defend the cell.
Future information about the role of DJ-1 may enable the development of drugs to
specifically target the protein, perhaps stopping or reversing Parkinson's
disease or Alzheimer's disease, which also may be impacted by the oxidation of
DJ-1. In the meantime, says Dr. Li, people looking to prevent neurological
degeneration might do well by looking to the kitchen cabinet, not the pharmacy:
green tea and vitamin C supplements are two bountiful sources of antioxidants.
(Opm. Uit eerder onderzoek is al gebleken dat verhoging van de glutathion waarden het DJ-1 proteïne kan activeren en daardoor de celdood van dopamine neuronen tegengaat. Meer over glutathion.)