What causes brain cell death in Parkinson’s patients

WASHINGTON - Researchers at The University of Texas Health Science Center have discovered a process that may begin to explain why the vast majority of Parkinson’s patients develop the progressive neurodegenerative disease.

The researchers demystified a process that leads to the death of brain cells - or neurons - in Parkinson’s patients. When researchers blocked the process, the neurons survived.

The findings could lead to an effective treatment to slow the progression of Parkinson’s disease, rather than simply address symptoms that include tremors, slowed movement, muscle stiffness and impaired balance. Further studies could lead to a diagnostic test that could screen for Parkinson’s years before symptoms develop, said Syed Z. Imam, adjunct assistant professor at the UT Health Science Center.

After analyzing cells and post-mortem brain tissue from animals and humans, researchers noted that oxidative stress - a known culprit in neuron death - activated a protein called tyrosine kinase c-Abl in the nigra-striatum area of the brain. Neurons in this part of the brain are particularly vulnerable to Parkinson’s injury.

Activation of this protein led to changes in another protein called parkin, which is known to be mutated in hereditary Parkinson’s. The altered parkin lacked the capacity to break down other proteins, leading to harmful clumps of unprocessed protein in the neuron. The scientists believe this accumulation leads to progressive neuron death, resulting in Parkinson’s symptoms that worsen over time.

“When we blocked tyrosine kinase c-Abl activation, parkin function was preserved and neurons were spared,” Imam said.

“We believe these studies provide sound rationale for moving forward with a preclinical trial of tyrosine kinase c-Abl inhibitors, with the goal of developing a potent therapeutic drug for slowing the progression of Parkinson’s.”

If preclinical trials in animal models of Parkinson’s disease yield positive results, the next step would be clinical trials in human patients, Imam said.

“The race is on to understand the mechanism of the 95 percent of Parkinson’s cases with no known cause, and our finding certainly is a building block,” Imam said.

“We have found a specific signaling mechanism that is only turned on by oxidative stress and is selective only to Parkinson’s-affected neurons of the nigra-striatum, which is the area that sends signals for balance to the cerebellum,” Imam added.

The study has been published in the Journal of Neuroscience. (ANI)