Scientists identify new lead in search for Parkinson's disease cure

Al Saint Jacques, MDLinx | October 07, 2016

Researchers have identified a protein that may lead to a new treatment for Parkinson’s disease, according to a paper published in the journal Nature Communications. Scientists from Iowa State University in Ames, Iowa; the University of Queensland, in Brisbane, Queensland, Australia; and the University of California, in Irvine, California, have identified a protein called Prokineticin-2 (PK2) that may protect brain cells and is expressed with greater frequency in the early stages of Parkinson’s disease.

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This diagram demonstrates how the neuropeptide Prokineticin-2 (PK2) is rapidly induced during early stages of neurotoxic stress and secreted into extracellular spaces.

“The neurons use PK2 to cope with stress. It’s an in-built protective mechanism,” explained Anumantha Kanthasamy, a Clarence Hartley Covault Distinguished Professor in veterinary medicine, the Eugene and Linda Lloyd Endowed Chair of Neurotoxicology, and chair of biomedical sciences at Iowa State University. Kanthasamy, one of the paper’s lead authors, has been working to understand the complex mechanisms of Parkinson’s disease and searching for a cure for the past two decades.

Anumantha Kanthasamy

PK2 works by stimulating the neurons to produce more mitochondria, the part of the cell that produces energy. The resulting improved energy production helps neurons withstand the ravages of the disease, which is a neurological disorder that results in insufficient levels of dopamine in the brain.

Parkinson’s disease is a progressive neurological disorder that takes years to develop. A better understanding of PK2 could provide a means of slowing development of the disease or lead to new therapies, Kanthasamy noted. For example, there may be ways to stimulate more production of the protein or protein analogs to bind with its receptors on neurons, he said.

The research team took a multidisciplinary and integrated approach to studying Parkinson’s disease. The scientists studied cultured brain cells, a rodent model, and post-mortem human brains to track changes brought on by Parkinson’s disease. Their research allowed them to confirm a high expression of PK2 in each facet of the study.

The discovery prompted the research team to investigate more thoroughly.

“Of the thousands and thousands of factors we tracked in our experiments, why was this protein expressed so highly?” explained Arthi Kanthasamy, a professor of biomedical sciences and Anumantha’s spouse. Finding the answer to that question poses a challenge that will take time to overcome, but the potential appears to be significant, she said.

The study was funded by a grant from the National Institutes of Health to Kanthasamy and Arthi Kanthasamy, a professor of biomedical sciences and Anumantha’s spouse. Six graduate students in Kanthasamy’s lab also contributed to the study, including co-first authors Richard Gordon and Matthew Neal, as well as researchers at other institutions.

Gordon, R. et al. Prokineticin-2 upregulation during neuronal injury mediates a compensatory protective response against dopaminergic neuronal degeneration. Nat. Commun. 7, 12932 doi: 10.1038/ncomms12932 (2016).

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