PMID- 37163909
OWN - NLM
STAT- MEDLINE
DCOM- 20230605
LR  - 20230606
IS  - 1872-6844 (Electronic)
IS  - 0920-1211 (Linking)
VI  - 193
DP  - 2023 Jul
TI  - Inhibition of mTORC2 improves brain injury in epileptic rats by promoting 
      chaperone-mediated autophagy.
PG  - 107161
LID - S0920-1211(23)00086-4 [pii]
LID - 10.1016/j.eplepsyres.2023.107161 [doi]
AB  - Epilepsy can seriously affect children's cognitive and behavioral development. 
      The mechanistic target of rapamycin(mTOR) pathway plays an important role in 
      neurodevelopment and epilepsy, but the mechanism of mechanistic target of 
      rapamycin complex 2 (mTORC2) in epilepsy is still unclear. Here, we compared the 
      similarities and differences of the mechanisms of action of mechanistic target of 
      rapamycin complex 1 (mTORC1) and mTORC2 complex in the pathogenesis of epilepsy. 
      Our research results show that the levels of apoptosis in cortical and 
      hippocampal neurons were upregulated in epileptic rats (F = 32.15, 30.96; both 
      P < 0.01), and epilepsy caused neuronal damage (F = 8.13, 9.43; both P < 0.01). 
      The mTORC2-Akt pathway was activated in the cortex and hippocampus of epileptic 
      rats. Inhibition of mTORC2 resulted in decreased levels of apoptosis and reduced 
      neuronal damage in the cortex and hippocampus of epileptic rats. In the 
      hippocampus, selective inhibition of mTORC2 increased lysosome-associated 
      membrane protein 2 A (LAMP2A) protein expression compared with the control group, 
      and the difference was statistically significant (F = 3.02, P < 0.05). Finally, 
      we concluded that in the hippocampus, selective inhibition of mTORC2 can improve 
      epileptic brain injury in rats by increasing chaperone-mediated autophagy (CMA) 
      levels.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Zhao, Yihan
AU  - Zhao Y
AD  - Department of Pediatrics, Peking University First Hospital, Beijing, China.
FAU - Zhao, Wenying
AU  - Zhao W
AD  - Department of Pediatrics, Peking University First Hospital, Beijing, China.
FAU - Han, Ying
AU  - Han Y
AD  - Department of Pediatrics, Peking University First Hospital, Beijing, China. 
      Electronic address: hanying1568@bjmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230505
PL  - Netherlands
TA  - Epilepsy Res
JT  - Epilepsy research
JID - 8703089
RN  - W36ZG6FT64 (Sirolimus)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
SB  - IM
MH  - Rats
MH  - Animals
MH  - Sirolimus/pharmacology
MH  - Mechanistic Target of Rapamycin Complex 2/metabolism
MH  - *Chaperone-Mediated Autophagy
MH  - Mechanistic Target of Rapamycin Complex 1/metabolism
MH  - *Brain Injuries
MH  - *Epilepsy/drug therapy
MH  - Autophagy
OTO - NOTNLM
OT  - Apoptosis
OT  - Autophagy
OT  - Epilepsy
OT  - Signaling pathway
OT  - mTOR
EDAT- 2023/05/11 00:41
MHDA- 2023/06/05 06:42
CRDT- 2023/05/10 18:05
PHST- 2023/01/06 00:00 [received]
PHST- 2023/03/22 00:00 [revised]
PHST- 2023/05/01 00:00 [accepted]
PHST- 2023/06/05 06:42 [medline]
PHST- 2023/05/11 00:41 [pubmed]
PHST- 2023/05/10 18:05 [entrez]
AID - S0920-1211(23)00086-4 [pii]
AID - 10.1016/j.eplepsyres.2023.107161 [doi]
PST - ppublish
SO  - Epilepsy Res. 2023 Jul;193:107161. doi: 10.1016/j.eplepsyres.2023.107161. Epub 
      2023 May 5.