$$News and Reports$$

Mar. 22, 2015
 

A collaborative research study recently published in the prestigious Cell Press journal Neuron by researchers from BGU and the University of California, San Diego, describes the identification of a novel molecular mechanism which could lead to the future development of new therapies for amyotrophic lateral sclerosis (ALS).  

ALS, also known as Lou Gehrig's disease, is a fatal neurodegenerative disease which involves the death of motor neurons that control voluntary muscles. ALS is characterized by progressive weakness and paralysis due to muscle atrophy. This leads to difficulty in speaking, swallowing, and eventually breathing. The cause of ALS is not known in about 90% of cases, but 10% of the cases are genetically inherited.The disease usually starts around the age of 40-60, and the average survival from onset to death is two to five years. About 10% survive longer than 10 years. Importantly, there is no cure or effective treatment for ALS. 

About 20% of the genetic cases are due to mutations in the superoxide dismutase (SOD1) gene. Multifaceted research projects have demonstrated that mutations in this gene (more than 165 different mutants are now known) provoke selective killing of motor neurons by their acquisition of some form of toxicity. However, the basis for this selective toxicity has not been identified. 

Recently, the findings of a collaborative research study conducted by the laboratory of Dr. Adrian Israelson (pictured above) from the Department of Physiology and Cell Biology at BGU and the group of Prof. Don W. Cleveland from the University of California, San Diego was published in the prestigious scientific journal Neuron. The researchers report the identification of a factor which is able to inhibit accumulation of misfolded SOD1. They purified it, and identified it to be the well-known multifunctional protein macrophage migration inhibitory factor (MIF). Purified MIF is shown to directly inhibit mutant SOD1 misfolding and binding to intracellular organelles. Elevated expression of MIF is shown to suppress accumulation of misfolded SOD1 in neuronal cells andextends survival of mutant SOD1 expressing motor neurons. These efforts identify low chaperone activity of MIF in motor neurons as a likely component of selective vulnerability to mutant SOD1 misfolding, and propose enhancement of intracellular MIF chaperone activity as an attractive therapeutic strategy.   

Since the misfolding of proteins is a common toxic mechanism among neurodegenerative disorders, this discovery by the Israelson and Cleveland laboratories holds the potential to serve as a target for novel therapeutic intervention aimed to raise the level of MIF within the central nervous system to treat not only ALS, but many other neurodegenerative diseases which are linked to accumulation of misfolded proteins.  

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Above: The Israelson lab team