title: TDP-43 proteinopathies: neurodegenerative protein misfolding diseases without amyloidosis.
abstract: In this review, we summarize recent advances in understanding frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS) and related neurodegenerative disorders that are collectively known as TDP-43 proteinopathies, since transactive response DNA-binding protein 43 (TDP-43) was recently shown to be the major component of the ubiquitinated inclusions that are their pathological hallmarks. TDP-43 proteinopathies are distinct from most other neurodegenerative disorders because TDP-43 inclusions are not amyloid deposits. Besides TDP-43-positive inclusions, both sporadic and familial forms of FTLD and ALS have the pathologic TDP-43 signature of abnormal hyperphosphorylation, ubiquitination and C-terminal fragments in affected brain and spinal cord, suggesting that they share a common mechanism of pathogenesis. Thus, these findings support the concept that FTLD and ALS represent a clinicopathologic spectrum of one disease, that is, TDP-43 proteinopathy.
authors: Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4283, USA.
authors: Linda K
authors: LK
authors: Kwong
authors: Kunihiro
authors: K
authors: Uryu
authors: John Q
authors: JQ
authors: Trojanowski
authors: Virginia M-Y
authors: VM
authors: Lee
mesh_terms: D000686:Amyloidosis; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D017510:Protein Folding; D025801:Ubiquitin
chemical_list: D004268:DNA-Binding Proteins; D025801:Ubiquitin