TDP-43
A decade ago, scientists identified mutations in TDP-43 as a relatively common genetic cause of ALS.
TDP-43 directs the production of proteins that bind RNA. RNA directs the assembly of proteins from amino acids and helps to shape the final product. Scientists suspect that mutations in TDP-43 somehow upsets this process.
Packard investigators are especially eager to discover exactly how mutant TDP-43 damages cells, to see if it does, indeed, upset RNA metabolism. That’s because their earlier discovery of ALS excitotoxicity showed that faulty RNA metabolism plays a major part in that greatly destructive process. Being able to link a mutant gene to one of the most cell-damaging happenings in ALS would be the most important find in ALS pathology research to date.
Mutations in the gene coding for TDP-43 also causes clumps or aggregates in motor neurons. Alzheimer’s and Parkinson’s diseases also involve toxic protein aggregates in nervous system cells.
Forming aggregates is an important sign. But what most excites Packard and other scientists is that TDP-43 mutations have been identified both in familial and in sporadic ALS patients.
As it is, TDP-43 has the potential to lead to an entirely different set of scientific observations, not to mention finding biomarkers for ALS, improved imaging of the disease and new animal models. All of that would set us more firmly on a road to therapy.
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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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