Toxic form of a protein called Elk-1, connects three serious neurodegenerative disorders.

As we age, our brain also changes, like rest of our body.  These changes in the brain are characterized by slowed thinking, occasional problems with remembering things.  However, serious memory loss, confusion and other major changes in the way our minds work are not a normal part of aging. They may be indications of failing brain cells. Here comes the serious neurodegenerative disorders.  Neurodegenerative brain disorders is the umbrella term for the progressive loss of structure or function of neurons, including death of neurons. Many neurodegenerative diseases including Parkinson’s, Alsheimer’s and Huntington’s occur as a result of neurodegenerative processes. As research progresses, many similarities appear which relate these diseases to one another on a sub-cellular level.

A research team from the University of Pennsylvania School of Medicine have found that the toxic form of a protein called Elk-1, connect the above mentioned degenerative brain disorders.  Usually in Parkinsons, Alzheimers and Huntington’s diseses, the protein Elk-1 appears to be  in clumps of misshaped form.  It is known that the transcription factor Elk-1 resides in both nuclear and extranuclear neuronal compartments, but when present in nerve cell dendrites it can trigger neuronal death.

In the current study,  the team used phototransfection to focally introduce and express small amounts of Elk-1 mRNA into various compartments of a single primary hippocampal neuron.  The researchers succeeded in determining the importance of this specific modification of Elk-1 on its ability to initiate regionalized cell death. The study conclude that a specific position on the protein could be modified in the dendrite to cause neuronal cell death.  Inorder to uncover a promising link between these diseases and normal and abnormal Elk-1, they screened tissue from a post-mortem human brain bank, , specifically samples representative of the three major neurodegenerative diseases. Also they found that they pElk-1 strongly associates with the pathological markers present in cases of Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease versus disease-free tissue.

The researchers now hopes to develop these initial findings to a larger sample size of tissues from neurodegenerative disease banks, and to screen blood samples from affected individuals to assess the biomarker capacity of this form of Elk-1 and to use animal models of these illnesses to assess the biological role of this modified form of Elk-1 in the disease processes. Also they aims to find other sites of toxic changes on the Elk-1 protein and will look in other disease tissue for modified Elk-1. The study was funded by the National Institute on Aging and the National Institute of Mental Health.

“These results suggest a molecular link between the presence of inclusions and neuronal loss that is shared across a spectrum of neurodegenerative disease,” notes senior author, James Eberwine, PhD, co-director of the Penn Genome Frontiers Institute and the Elmer Holmes Bobst Professor of Pharmacology. “Identifying these links within the diseased microenvironment will open up novel avenues for therapeutic intervention. For example it is reasonable to now ask, “Is this molecule a possible new biomarker for these neurodegenerative diseases?” says Eberwine.