Open AccessTDP-43 Proteinopathies: Neurodegenerative Protein Misfolding Diseases without Amyloidosis
Author(s) -
Linda K. Kwong,
Kunihiro Uryu,
John Q. Trojanowski,
Virginia M.Y. Lee
Publication year - 2007
Publication title -
neurosignals
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 0.755
H-Index - 67
eISSN - 1424-8638
pISSN - 1424-862X
DOI - 10.1159/000109758
Subject(s) - frontotemporal lobar degeneration , amyotrophic lateral sclerosis , ubiquitin , neurodegeneration , pathogenesis , neuroscience , medicine , disease , amyloidosis , pathology , hyperphosphorylation , amyloid (mycology) , frontotemporal dementia , biology , dementia , kinase , genetics , gene
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.