Abstract
Purpose of review: We examine current evidence that the transactive response DNA-binding protein (TDP-43) plays a pathogenic role in both amyotrophic lateral sclerosis and frontotemporal dementia. Recent findings: TDP-43 was recently identified as the major pathological protein in sporadic amyotrophic lateral sclerosis and in the most common pathological subtype of frontotemporal dementia, frontotemporal lobar degeneration with ubiquitinated inclusions. In these conditions, abnormal C-terminal fragments of TDP-43 are ubiquitinated, hyperphosphorylated and accumulate as cellular inclusions in neurons and glia. Cells with inclusions show absence of the normal nuclear TDP-43 localization. Recently, missense mutations in the gene encoding TDP-43 have been identified in patients with sporadic and familial amyotrophic lateral sclerosis. Summary: The recent discovery of pathological TDP-43 in both amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitinated inclusions confirms that these are closely related conditions within a new biochemical class of neurodegenerative disease, the TDP-43 proteinopathies.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 693-700 |
| Number of pages | 8 |
| Journal | Current Opinion in Neurology |
| Volume | 21 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 2008 |
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Keywords
- Amyotrophic lateral sclerosis
- Frontotemporal dementia
- Frontotemporal lobar degeneration with ubiquitinated inclusions
- Transactive response DNA-binding protein-43
ASJC Scopus subject areas
- Clinical Neurology
- Neurology
Cite this
The role of transactive response DNA-binding protein-43 in amyotrophic lateral sclerosis and frontotemporal dementia. / Mackenzie, Ian R A; Rademakers, Rosa V.
In: Current Opinion in Neurology, Vol. 21, No. 6, 12.2008, p. 693-700.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The role of transactive response DNA-binding protein-43 in amyotrophic lateral sclerosis and frontotemporal dementia
AU - Mackenzie, Ian R A
AU - Rademakers, Rosa V
PY - 2008/12
Y1 - 2008/12
N2 - Purpose of review: We examine current evidence that the transactive response DNA-binding protein (TDP-43) plays a pathogenic role in both amyotrophic lateral sclerosis and frontotemporal dementia. Recent findings: TDP-43 was recently identified as the major pathological protein in sporadic amyotrophic lateral sclerosis and in the most common pathological subtype of frontotemporal dementia, frontotemporal lobar degeneration with ubiquitinated inclusions. In these conditions, abnormal C-terminal fragments of TDP-43 are ubiquitinated, hyperphosphorylated and accumulate as cellular inclusions in neurons and glia. Cells with inclusions show absence of the normal nuclear TDP-43 localization. Recently, missense mutations in the gene encoding TDP-43 have been identified in patients with sporadic and familial amyotrophic lateral sclerosis. Summary: The recent discovery of pathological TDP-43 in both amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitinated inclusions confirms that these are closely related conditions within a new biochemical class of neurodegenerative disease, the TDP-43 proteinopathies.
AB - Purpose of review: We examine current evidence that the transactive response DNA-binding protein (TDP-43) plays a pathogenic role in both amyotrophic lateral sclerosis and frontotemporal dementia. Recent findings: TDP-43 was recently identified as the major pathological protein in sporadic amyotrophic lateral sclerosis and in the most common pathological subtype of frontotemporal dementia, frontotemporal lobar degeneration with ubiquitinated inclusions. In these conditions, abnormal C-terminal fragments of TDP-43 are ubiquitinated, hyperphosphorylated and accumulate as cellular inclusions in neurons and glia. Cells with inclusions show absence of the normal nuclear TDP-43 localization. Recently, missense mutations in the gene encoding TDP-43 have been identified in patients with sporadic and familial amyotrophic lateral sclerosis. Summary: The recent discovery of pathological TDP-43 in both amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitinated inclusions confirms that these are closely related conditions within a new biochemical class of neurodegenerative disease, the TDP-43 proteinopathies.
KW - Amyotrophic lateral sclerosis
KW - Frontotemporal dementia
KW - Frontotemporal lobar degeneration with ubiquitinated inclusions
KW - Transactive response DNA-binding protein-43
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U2 - 10.1097/WCO.0b013e3283168d1d
DO - 10.1097/WCO.0b013e3283168d1d
M3 - Article
C2 - 18989115
AN - SCOPUS:56749093062
VL - 21
SP - 693
EP - 700
JO - Current Opinion in Neurology
JF - Current Opinion in Neurology
SN - 1350-7540
IS - 6
ER -