Publication: Phosphorylated TDP-43 localizes to chronic cerebral infarctions in human brains
Authors
Umahara, Takahiko ; Uchihara, Toshiki ; Hirao, Kentaro ; Shimizu, Soichiro ; Hanyu, Haruo
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Publisher
Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/10.14670/HH-18-235
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info:eu-repo/semantics/article
Description
Abstract
The transactivation response DNA-binding
protein of 43 kDa (TDP-43) is a nuclear protein pivotal
in RNA processing. Because phosphorylated TDP43
(pTDP-43) has been identified as a component of the
ubiquitin-positive and tau-negative inclusions observed
in the brains of frontotemporal lobar degeneration
(FTLD) and amyotrophic lateral sclerosis (ALS)
patients, it is considered to play a major role in
neurodegenerative processes. We previously reported
that pTDP-43 is located in macrophages of
atherosclerotic lesions of human carotid and major
cerebral arteries. We hence hypothesized that pTDP-43
might be localized in the macrophages of other human
brain lesions. Therefore, we investigated the
immunolocalization of pTDP-43 in human brains with
chronic cerebral infarction. Furthermore, we investigated
the colocalization of pTDP-43 and the 14-3-3 eta
isoform and found that pTDP-43 was localized in many
macrophages located in chronic cerebral infarctions, in 6
out of the 15 human brains analyzed. pTDP-43
colocalized with the 14-3-3 eta isoform in these lesions.
This is the first demonstration of pTDP-43
immunolocalization in chronic cerebral infarctions in
human brains. We believe that our findings may be
useful towards further understanding the
pathophysiological roles of TDP-43 in various
neurological disorders.
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