12/6/2004

Protecting microtubule "highways" may lead to novel therapies, study shows". Parkinson's disease may be caused by an environmental-genetic whammy on the neurons that produce dopamine, the neurotransmitter that controls body movement, a new study has shown.

Researchers at the University at Buffalo, using cultures of rat neurons, have shown that the presence of mutated parkin genes, combined with the toxic effects of the chemical rotenone, results in a cascade of highly toxic free radicals, the destruction of microtubules that transport dopamine to the brain's movement center, and eventual death of the dopamine producing neurons.

When microtubules are broken down by rotenone, the disassociated protein building blocks, called tubulin, are left behind. These tubulins are probably misfolded proteins. Left unattended, they could interfere with the normal assembly of microtubules. Based on previous work that parkin marks this "old" tubulin for rapid degradation, we theorize that parkin may thus prevent this interference.

Mutated parkin loses this protective ability, however, allowing rotenone to do its damage unchecked.

Rotenenone damages the microtubules, which prevents dopamine from reaching the brain's movement center, causing a back-up in the dopamine traansport. Meanwhile the backed-up dopamine accummulates in the neuron's cytoplasm and breaks down, allowing the breakdown of toxic free radicals, which destroy the neurons.

Rick, this blows your BBB sky high. If the dopamine cannot get out of the substantia niagra it can't leak out of the brain barrier.

Those of us who have definite mutations, espiecially 2 or more, as I do, are the trunk of the tree. Because our Parkin gene is not acting to protect the microtubiles it was almost certain we would get Parkinson's. Each of the others who have been diagnosed with idiopathic Parkinson's are different limbs or branches who were exposed to a toxin or anoxic brain damage The tree is huge with many different branches joining to limbs then joining with the trunk.

There are many different paths to Parkinson's disease. We can follow each and every branch to the limb to find the source of one shared cause, then follow the limbs to the trunk to find more about the etiology of Parkinson's disease.

Or research could focus on the trunk of the tree and find a way to make the trunk healthy again, hense, the limbs and branches would follow. All of you can make your choice of how to effectively research the etiology and eventual cure for Parkinson's disease. Either focus your funds toward the trunk or do what is being done now. Chase each and every branch throwing money at them, hoping to get lucky and find a cure for a few while never finding the etiology of the making of Parkinson's disease.