THURSDAY, Oct. 5 (HealthDay News) -- Researchers have discovered that TDP-43 is the major ubiquitinated and aggregated protein found in neurodegenerative diseases including frontotemporal lobar degeneration and amyotrophic lateral sclerosis (ALS), according to a report in the Oct. 6 issue of Science.
Virginia M.-Y. Lee, Ph.D., of the University of Pennsylvania School of Medicine in Philadelphia, and colleagues used mass spectrometry to identify immunoreactive proteins found in ubiquitinated and misfolded protein aggregates recovered from the frontal lobe of ALS and frontotemporal lobar degeneration (FTLD-U) patients.
The investigators found that TDP-43 that was highly modified by phosphorylation, ubiquitination and C-terminal cleavage could be recovered from affected central nervous system tissue, including spinal cord, hippocampus and neocortex, but not normal tissue.
"The identification of TDP-43 as the major component of [ubiquinated disease proteins] specific to sporadic and familial FTLD-U as well as sporadic ALS resolves a long-standing enigma concerning the nature of the ubiquitinated disease protein in these disorders," the authors write. "These insightsÂ…can accelerate efforts to develop better therapies for these disorders."
Abstract
Full Text (subscription or payment may be required)
