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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Sci+Rep
2016 ; 6
(ä): 33176
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Bexarotene targets autophagy and is protective against thromboembolic stroke in
aged mice with tauopathy
#MMPMID27624652
Huuskonen MT
; Loppi S
; Dhungana H
; Keksa-Goldsteine V
; Lemarchant S
; Korhonen P
; Wojciechowski S
; Pollari E
; Valonen P
; Koponen J
; Takashima A
; Landreth G
; Goldsteins G
; Malm T
; Koistinaho J
; Kanninen KM
Sci Rep
2016[Sep]; 6
(ä): 33176
PMID27624652
show ga
Stroke is a highly debilitating, often fatal disorder for which current therapies
are suitable for only a minor fraction of patients. Discovery of novel, effective
therapies is hampered by the fact that advanced age, primary age-related
tauopathy or comorbidities typical to several types of dementing diseases are
usually not taken into account in preclinical studies, which predominantly use
young, healthy rodents. Here we investigated for the first time the
neuroprotective potential of bexarotene, an FDA-approved agent, in a co-morbidity
model of stroke that combines high age and tauopathy with thromboembolic cerebral
ischemia. Following thromboembolic stroke bexarotene enhanced autophagy in the
ischemic brain concomitantly with a reduction in lesion volume and amelioration
of behavioral deficits in aged transgenic mice expressing the human P301L-Tau
mutation. In in vitro studies bexarotene increased the expression of autophagy
markers and reduced autophagic flux in neuronal cells expressing P301L-Tau.
Bexarotene also restored mitochondrial respiration deficits in P301L-Tau neurons.
These newly described actions of bexarotene add to the growing amount of
compelling data showing that bexarotene is a potent neuroprotective agent, and
identify a novel autophagy-modulating effect of bexarotene.
|Aging
[MESH]
|Animals
[MESH]
|Autophagy/*drug effects
[MESH]
|Bexarotene
[MESH]
|Mice
[MESH]
|Mice, Transgenic
[MESH]
|Neuroprotective Agents/*pharmacology
[MESH]
|Stroke/metabolism/pathology/*prevention & control
[MESH]