A team of researchers have unveiled a process which places neurons at risk of cell death. This finding characterizes numerous neurodegenerative diseases and emphasizes the connection between several proteins known to go awry in ALS and a related disease, frontotemporal dementia (FTD). This research appears in today's edition of the Proceedings of the National Academy of Sciences.
The first protein involved is TDP-43; a lack of this protein has been shown to cause both ALS and FTD. This study revealed that when there is a dearth of TDP-43, a second protein, sortilin, is made in excess. Researchers found some copies of that protein are defective.
"This new finding puts together several critical links in the chain leading to neuronal death," said Lucie Bruijn, Ph.D., Chief Scientist for The ALS Association.
In this process, normal and defective sortilin bind to another protein, progranulin, a neuronal growth factor. When excess, normal sortilin and the defective sortilin bind to progranulin, neurons become deprived of the vital growth factor. In sum, a lack of TDP-43 leads to excessive normal and defective sortilin, which decreases the amount of neuroprotective progranulin. This shortage of progranulin causes neurons to die.
The ALS Association has supported the researchers who led the study, which include Mercedes Prudencio, Ph.D., and Leonard Petrucelli, Ph.D., of the Mayo Clinic in Jacksonville, Florida, and Emanuele Buratti, Ph.D., of the International Center for Genetic Engineering and Biotechnology in Trieste, Italy.
“We are extremely pleased that our support has helped Dr. Prudencio advance the field through this research,” Dr. Bruijn said. “The discovery of this mechanism is important for understanding how neurons die in ALS and FTD, and in the development of new therapies targeting this pathway.”
In 2011, Dr. Prudencio received The Association’s Milton Safenowitz Post-Doctoral Fellowship for ALS Research. The ALS Association is especially committed to bringing new concepts and methods into ALS research, and young scientists play an important role in this process. Funding is generously provided by the Safenowitz family through the Greater New York Chapter of The ALS Association, in memory of Safenowitz, who died in 1998 of the disease.
The Association's Minnesota/North Dakota/South Dakota Chapter also helped to fund this research.