Study finds a link between brain diseases

A recent Penn-led study identified a particularly toxic form of the protein Elk-1, which provides clues to the first link between Huntington’s, Parkinson’s and Alzheimer’s diseases.

Researchers from the School of Medicine and the University of Rochester began with the knowledge — derived from past experimentation — that when a modified form of this protein, phospho-Elk-1, is located in the dendrite of a neuron, it is able to initiate cell death.

“This was the first protein that tied these three diseases together,” said James Eberwine, the senior author of the study and the co-director of the Penn Genome Frontier Institute. “If this protein is indeed important to the neurodegenerative process, we would be able to look at phospho-Elk-1 as an early indicator of these diseases.”

After inserting mutated Elk-1 into dendrites and cell bodies, the researchers were able to prove that this protein could be manipulated in the dendrite to cause the death of a cell.

The authors of this study then compared levels of phospho-Elk-1 in tissue afflicted by Alzheimer’s, Parkinson’s and Huntington’s diseases and realized that this particular protein was significantly more present in the diseased tissues than disease-free tissue.

Professor of Pharmacology Jai-Yoon Sul, a fellow author of the study, said, “Elk-1 is one of the first proteins that has defined function in the cell in terms of neurodegenerative disease markers … It isn’t just a pathological marker, but also has the function of collapsing the dendrite and killing the cell.”

Eberwine added that if the researchers can identify the specific enzymes — called protein kinases — that cause Elk-1 to mutate in this manner, “there might be reasonable therapeutic topics” that could aid people inflicted with these diseases.

“We could do drug screens to see if we could modulate the kinase activity so that we would no longer get cell death or clumps of proteins that are characteristic of these neurodegenerative diseases,” he said.

However, Eberwine said while the study showed correlation, it did not prove that this protein caused the three neurodegenerative diseases.

In addition, Eberwine and Sul emphasized that this study will not lead to a complete cure for Alzheimer’s, Huntington’s or Parkinson’s, since these diseases are caused by genetic defects that are very difficult to reverse.

However, the study does lay foundations for future studies examining therapeutic interventions that would be able to delay the onset of the symptoms of these diseases.

“Anything that leads toward understanding diseases and making their symptoms less severe can save money, time, and create a better lifestyle for those who are inflicted,” Eberwine said. “If you can delay the onset of the disease for just four or five years, you’ve saved trillions in healthcare dollars.”

Eberwine and Sul’s findings were published in the beginning of February in the online journal PLoS One. The study was funded by the National Institute on Aging and the National Institute of Mental Health, according to a Penn Med press release.

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