title: TDP-43: a novel neurodegenerative proteinopathy.
abstract: Over the past decade, it has become clear that there is a significant overlap in the clinical spectrum of frontotemporal lobar degeneration and amyotrophic lateral sclerosis (ALS). The identification of TDP-43 as the major disease protein in the pathology of both frontotemporal lobar degeneration with ubiquitin inclusions and ALS provides the first molecular link for these diseases. Pathological TDP-43 is abnormally phosphorylated, ubiquitinated, and cleaved to generate carboxy-terminal fragments in affected brain regions. The normal nuclear expression of TDP-43 is also reduced leading to the hypothesis that sequestration of TDP-43 in pathological inclusions contributes to disease pathogenesis. Thus, TDP-43 is the newest member of the growing list of neurodegenerative proteinopathies, but unique in that it lacks features of brain amyloidosis.
authors.affiliation: Department of Pathology & Laboratory Medicine and Institute on Aging, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, United States.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Forman
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003704:Dementia / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D025801:Ubiquitin