Another piece to Parkinson’s puzzle

IOWA STATE (US) — There’s hope that a newly discovered protein pathway could lead to a much clearer understanding of Parkinson’s disease.

Anumantha Kanthasamy, a professor of biomedical sciences and chair of neurotoxicology at Iowa State University, has been working to understand the complex mechanisms of the disease for more than a decade. He believes this recent discovery offers hope for a cure.

Parkinson’s disease sufferers lack a sufficient amount of a brain chemical called dopamine. In previous research, Kanthasamy has shown that a novel protein—known as protein kinase-C (specifically PKCδ)—kills essential dopamine-producing cells in the brain.

Now, Kanthasamy has shown how to modify the production of the kinase-C—and how to inhibit it. The research is reported in the Journal of Neuroscience.

The process begins with a protein called alpha-synuclein (ά-synuclein) that—after interacting with other proteins in cells—becomes part of the protein complex that modifies kinase-C level in the cells.

One of the proteins that alpha-synuclein interacts with inside the cell is known as p300. By changing the activity of p300 protein, Kanthasamy believes that production of the destructive kinase-C will be inhibited.

“We have identified an essential pathway that regulates the survival of dopamine-producing nerve cells,” he says.

“This p300 is an intermediate protein that is implicit in the Parkinson’s disease,” Kanthasamy adds. “By modifying this protein, we can potentially reduce the expression of kinase-C and the associated destructive effects on dopamine-producing cells.”

“We found the mechanism,” says Kanthasamy of the pathway. “Now we can focus on finding chemicals that may be able to control the mechanism.”

Parkinson’s disease strikes around 50,000 people each year. Currently about 1 million people have the disease, including actor Michael J. Fox and former boxing champion Muhammad Ali.

Currently, there is no cure for Parkinson’s and available therapies only treat the symptoms, which include trembling in hands, arms, legs, jaw, and face; rigidity or stiffness of the limbs and trunk; slowness of movement; and impaired balance and coordination.

As these symptoms become more pronounced, patients may have difficulty walking, talking, or completing other simple tasks. Because the disease typically affects people over the age of 50, the National Institutes of Health, which funded the study, anticipates the incidence of Parkinson’s will increase as the nation’s population ages.

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