PMID- 34073791
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210626
IS  - 2227-9059 (Print)
IS  - 2227-9059 (Electronic)
IS  - 2227-9059 (Linking)
VI  - 9
IP  - 6
DP  - 2021 May 24
TI  - Involvement of mTOR Pathways in Recovery from Spinal Cord Injury by Modulation of 
      Autophagy and Immune Response.
LID - 10.3390/biomedicines9060593 [doi]
LID - 593
AB  - Traumatic spinal cord injury (SCI) is untreatable and remains the leading cause 
      of disability. Neuroprotection and recovery after SCI can be partially achieved 
      by rapamycin (RAPA) treatment, an inhibitor of mTORC1, complex 1 of the mammalian 
      target of rapamycin (mTOR) pathway. However, mechanisms regulated by the mTOR 
      pathway are not only controlled by mTORC1, but also by a second mTOR complex 
      (mTORC2). Second-generation inhibitor, pp242, inhibits both mTORC1 and mtORC2, 
      which led us to explore its therapeutic potential after SCI and compare it to 
      RAPA treatment. In a rat balloon-compression model of SCI, the effect of daily 
      RAPA (5 mg/kg; IP) and pp242 (5 mg/kg; IP) treatment on inflammatory responses 
      and autophagy was observed. We demonstrated inhibition of the mTOR pathway after 
      SCI through analysis of p-S6, p-Akt, and p-4E-BP1 levels. Several proinflammatory 
      cytokines were elevated in pp242-treated rats, while RAPA treatment led to a 
      decrease in proinflammatory cytokines. Both RAPA and pp242 treatments caused an 
      upregulation of LC3B and led to improved functional and structural recovery in 
      acute SCI compared to the controls, however, a greater axonal sprouting was seen 
      following RAPA treatment. These results suggest that dual mTOR inhibition by 
      pp242 after SCI induces distinct mechanisms and leads to recovery somewhat 
      inferior to that following RAPA treatment.
FAU - Vargova, Ingrid
AU  - Vargova I
AD  - Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 
      Videnska, 1083, 142 20 Prague, Czech Republic.
AD  - 2nd Faculty of Medicine, Charles University, V Uvalu 84, 150 06 Prague, Czech 
      Republic.
FAU - Machova Urdzikova, Lucia
AU  - Machova Urdzikova L
AD  - Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 
      Videnska, 1083, 142 20 Prague, Czech Republic.
FAU - Karova, Kristyna
AU  - Karova K
AD  - Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 
      Videnska, 1083, 142 20 Prague, Czech Republic.
FAU - Smejkalova, Barbora
AU  - Smejkalova B
AUID- ORCID: 0000-0002-4812-9458
AD  - Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 
      Videnska, 1083, 142 20 Prague, Czech Republic.
AD  - 2nd Faculty of Medicine, Charles University, V Uvalu 84, 150 06 Prague, Czech 
      Republic.
FAU - Sursal, Tolga
AU  - Sursal T
AD  - Department of Neurosurgery, Westchester Medical Center, New York Medical College, 
      Valhalla, NY 10595, USA.
FAU - Cimermanova, Veronika
AU  - Cimermanova V
AD  - Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 
      Videnska, 1083, 142 20 Prague, Czech Republic.
FAU - Turnovcova, Karolina
AU  - Turnovcova K
AD  - Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 
      Videnska, 1083, 142 20 Prague, Czech Republic.
FAU - Gandhi, Chirag D
AU  - Gandhi CD
AD  - Department of Neurosurgery, Westchester Medical Center, New York Medical College, 
      Valhalla, NY 10595, USA.
FAU - Jhanwar-Uniyal, Meena
AU  - Jhanwar-Uniyal M
AD  - Department of Neurosurgery, Westchester Medical Center, New York Medical College, 
      Valhalla, NY 10595, USA.
FAU - Jendelova, Pavla
AU  - Jendelova P
AUID- ORCID: 0000-0002-4644-9212
AD  - Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, 
      Videnska, 1083, 142 20 Prague, Czech Republic.
AD  - 2nd Faculty of Medicine, Charles University, V Uvalu 84, 150 06 Prague, Czech 
      Republic.
LA  - eng
GR  - CZ.02.1.01/0.0./0.0/15_003/0000419/Ministerstvo Skolstvi, Mladeze a Telovychovy/
GR  - LTAUSA17120/Ministerstvo Skolstvi, Mladeze a Telovychovy/
PT  - Journal Article
DEP - 20210524
PL  - Switzerland
TA  - Biomedicines
JT  - Biomedicines
JID - 101691304
PMC - PMC8225190
OTO - NOTNLM
OT  - autophagy
OT  - dual inhibition
OT  - inflammation
OT  - mTOR
OT  - pp242
OT  - rapamycin
OT  - spinal cord injury
COIS- The authors declare no conflict of interest.
EDAT- 2021/06/03 06:00
MHDA- 2021/06/03 06:01
PMCR- 2021/05/24
CRDT- 2021/06/02 01:39
PHST- 2021/02/28 00:00 [received]
PHST- 2021/05/17 00:00 [revised]
PHST- 2021/05/20 00:00 [accepted]
PHST- 2021/06/02 01:39 [entrez]
PHST- 2021/06/03 06:00 [pubmed]
PHST- 2021/06/03 06:01 [medline]
PHST- 2021/05/24 00:00 [pmc-release]
AID - biomedicines9060593 [pii]
AID - biomedicines-09-00593 [pii]
AID - 10.3390/biomedicines9060593 [doi]
PST - epublish
SO  - Biomedicines. 2021 May 24;9(6):593. doi: 10.3390/biomedicines9060593.