Benomyl


Many studies in the past decade have pointed out that pesticides are the underlying cause of Parkinson’s disease, which is a neurodegenerative disease that impairs motor function and afflicts one million Americans. However, scientists do not yet have a good understanding of how these chemicals damage the brain. A recent study suggests a possible answer: pesticides may inhibit the biochemical pathways that normally protect dopaminergic neurons, which are brain cells that are selectively attacked by diseases. Preliminary studies have also shown that this approach can play a role in Parkinson’s disease even without the use of pesticides, providing exciting new targets for drug development.
Past studies have shown that a pesticide called benomyl, even though it was banned in the United States for health concerns in 2001, still lingers in the environment. It inhibits aldehyde dehydrogenase in the liver ( ALDH) chemical activity. Researchers at the University of California, Los Angeles, University of California, Berkeley, California Institute of Technology, and the Veterans Affairs Medical Center of Greater Los Angeles wanted to know whether this pesticide would also affect the level of ALDH in the brain. ALDH’s job is to decompose the naturally occurring toxic chemical DOPAL to make it harmless.
To find out, the researchers exposed different types of human brain cells and later entire zebrafish to benomyl. Their lead author and University of California, Los Angeles (UCLA) neurologist Jeff Bronstein (Jeff Bronstein) stated that they found that it “killed almost half of dopamine neurons, while all other neurons were untested.” “When they zeroed on the affected cells, they confirmed that benomyl indeed inhibited the activity of ALDH, thereby stimulating the toxic accumulation of DOPAL. Interestingly, when scientists used another technique to reduce DOPAL levels, benomyl did not harm dopamine neurons. This finding suggests that the pesticide specifically kills these neurons because it allows DOPAL to accumulate.
Since other pesticides also inhibit the activity of ALDH, Bronstein speculates that this approach can help explain the link between Parkinson’s disease and general pesticides. More importantly, studies have found that DOPAL activity is very high in the brains of Parkinson’s disease patients. These patients have not been highly exposed to pesticides. Therefore, regardless of the cause, this biochemical cascade process may participate in the disease process. If this is true, then drugs that block or clear DOPAL in the brain may prove to be a promising treatment for Parkinson’s disease.