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Cell Death Pathways

Every cell in the body has a built-in suicide program that’s normally kept under control. Programmed cell death, known as apoptosis, can occur at various stages during development, or when a cell becomes too damaged by infection, cancer, or old age.

Studies by Packard scientists and others show that in ALS, however, this process occurs prematurely. In the SOD1 mouse model of the disease, scientists have verified that motor neurons ultimately die via apoptosis. More recent work by our researchers shows that the continued, early activation of apoptosis pathways occurs before ALS symptoms appear in the model mice. The end stages of the process are turned on shortly before motor neuron death.

Drugs that inhibit apoptosis have shown some success in ALS mice by delaying disease onset and progress. These agents are not yet available for human use, although many companies are beginning to develop them. Understanding cell death pathways is an active area for future ALS research at both the basic science and the therapeutic level.

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Johns Hopkins University
Motor neurons can only work properly if the cell’s proteins can get to the right place at the right time. Thomas Lloyd uses the fruit fly Drosophila melanogaster to study how proteins are shuttled between the cell body and the synapse, as interruptions in this process have been linked to ALS. 
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University of Michigan
Sami Barmada wants to answer a very basic question about ALS: why motor neurons? Of all the different types of neurons in the body (and scientists estimate there are probably several hundred), it’s only motor neurons that are affected in ALS. Knowing why this is, Barmada believes, could be the key to developing new potential treatments that could prevent the deterioration and death of motor neurons. 
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