Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.11.27 (
AMPK
)
6,299
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Background and Aim:
Increasing evidence suggests that spinal cord injury (SCI)-induced defects in autophagic flux may contribute to an impaired ability for neurological repair following injury.
Transcription factor E3
(
TFE3
) plays a crucial role in oxidative metabolism, lysosomal homeostasis, and autophagy induction. Here, we investigated the role of
TFE3
in modulating autophagy following SCI and explored its impact on neurological recovery.
Methods:
Histological analysis via HE, Nissl and Mason staining, survival rate analysis, and behavioral testing via BMS and footprint analysis were used to determine functional recovery after SCI. Quantitative real-time polymerase chain reaction, Western blotting, immunofluorescence, TUNEL staining, enzyme-linked immunosorbent assays, and immunoprecipitation were applied to examine levels of autophagy flux, ER-stress-induced apoptosis, oxidative stress, and
AMPK
related signaling pathways.
In vitro
studies using PC12 cells were performed to discern the relationship between ROS accumulation and autophagy flux blockade.
Results:
Our results showed that in SCI, defects in autophagy flux contributes to ER stress, leading to neuronal death. Furthermore, SCI enhances the production of reactive oxygen species (ROS) that induce lysosomal dysfunction to impair autophagy flux. We also showed that
TFE3
levels are inversely correlated with ROS levels, and increased
TFE3
levels can lead to improved outcomes. Finally, we showed that activation of
TFE3
after SCI is partly regulated by
AMPK
-mTOR and
AMPK
-SKP2-CARM1 signaling pathways.
Conclusions:
TFE3
is an important regulator in ROS-mediated autophagy dysfunction following SCI, and
TFE3
may serve as a promising target for developing treatments for SCI.
...
PMID:TFE3, a potential therapeutic target for Spinal Cord Injury via augmenting autophagy flux and alleviating ER stress. 3280 92
