A new study by researchers at the OHSU School of Dentistry advances our understanding of how a protein, TDP-43, impacts gene expression in neurodegenerative diseases like ALS. The researchers altered levels of TDP-43 in fruit flies to directly compare too much versus too little of the protein. Using massively parallel sequencing, they found that loss of TDP-43 results in widespread gene activation and altered splicing. Over expression resulted in decreased gene expression–a finding contrary to previous studies that indicated both loss-of-function and over expression may cause ALS.
This study was supported by grants from the National Institutes of Health (NS071186); the ALS Association; and the Muscular Dystrophy Association.