PMID- 36678636
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230201
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 15
IP  - 1
DP  - 2022 Dec 20
TI  - Combination of a Chaperone Synthesis Inducer and an Inhibitor of GAPDH 
      Aggregation for Rehabilitation after Traumatic Brain Injury: A Pilot Study.
LID - 10.3390/pharmaceutics15010007 [doi]
LID - 7
AB  - The recovery period after traumatic brain injury (TBI) is often complicated by 
      secondary damage that may last for days or even months after trauma. Two 
      proteins, Hsp70 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), were 
      recently described as modulating post-traumatic processes, and in this study, we 
      test them as targets for combination therapy using an inhibitor of GAPDH 
      aggregation (derivative of hydrocortisone RX624) and an inducer of Hsp70 
      synthesis (the pyrrolylazine derivative PQ-29). The protective effect of the 
      combination on C6 rat glioblastoma cells treated with the cerebrospinal fluid of 
      traumatized animals resulted in an increase in the cell index and in a reduced 
      level of apoptosis. Using a rat weight drop model of TBI, we found that the 
      combined use of both drugs prevented memory impairment and motor deficits, as 
      well as a reduction of neurons and accumulation of GAPDH aggregates in brain 
      tissue. In conclusion, we developed and tested a new approach to the treatment of 
      TBI based on influencing distinct molecular mechanisms in brain cells.
FAU - Dutysheva, Elizaveta A
AU  - Dutysheva EA
AD  - Institute of Cytology of the Russian Academy of Sciences, 194064 St. Petersburg, 
      Russia.
FAU - Mikhaylova, Elena R
AU  - Mikhaylova ER
AD  - Institute of Cytology of the Russian Academy of Sciences, 194064 St. Petersburg, 
      Russia.
FAU - Trestsova, Maria A
AU  - Trestsova MA
AD  - Department of Organic and Biomolecular Chemistry, Ural Federal University, 620002 
      Ekaterinburg, Russia.
FAU - Andreev, Alexander I
AU  - Andreev AI
AD  - Laboratory of Experimental Pharmacology, Perm State University, 614990 Perm, 
      Russia.
AD  - Perm State Pharmaceutical Academy, 614990 Perm, Russia.
FAU - Apushkin, Danila Yu
AU  - Apushkin DY
AUID- ORCID: 0000-0003-4459-5264
AD  - Laboratory of Experimental Pharmacology, Perm State University, 614990 Perm, 
      Russia.
AD  - Perm State Pharmaceutical Academy, 614990 Perm, Russia.
FAU - Utepova, Irina A
AU  - Utepova IA
AD  - Department of Organic and Biomolecular Chemistry, Ural Federal University, 620002 
      Ekaterinburg, Russia.
AD  - Postovsky Institute of Organic Synthesis, Ural Branch, The Russian Academy of 
      Sciences, 620108 Ekaterinburg, Russia.
FAU - Serebrennikova, Polina O
AU  - Serebrennikova PO
AD  - Department of Organic and Biomolecular Chemistry, Ural Federal University, 620002 
      Ekaterinburg, Russia.
FAU - Akhremenko, Eugenia A
AU  - Akhremenko EA
AUID- ORCID: 0000-0003-0757-064X
AD  - Laboratory of Experimental Pharmacology, Perm State University, 614990 Perm, 
      Russia.
FAU - Aksenov, Nikolay D
AU  - Aksenov ND
AD  - Institute of Cytology of the Russian Academy of Sciences, 194064 St. Petersburg, 
      Russia.
FAU - Bon', Elizaveta I
AU  - Bon' EI
AD  - Department of Histology, Cytology and Embryology, Grodno State Medical 
      University, 230009 Grodno, Belarus.
FAU - Zimatkin, Sergey M
AU  - Zimatkin SM
AD  - Department of Histology, Cytology and Embryology, Grodno State Medical 
      University, 230009 Grodno, Belarus.
FAU - Chupakhin, Oleg N
AU  - Chupakhin ON
AD  - Department of Organic and Biomolecular Chemistry, Ural Federal University, 620002 
      Ekaterinburg, Russia.
AD  - Postovsky Institute of Organic Synthesis, Ural Branch, The Russian Academy of 
      Sciences, 620108 Ekaterinburg, Russia.
FAU - Margulis, Boris A
AU  - Margulis BA
AD  - Institute of Cytology of the Russian Academy of Sciences, 194064 St. Petersburg, 
      Russia.
FAU - Guzhova, Irina V
AU  - Guzhova IV
AUID- ORCID: 0000-0002-8775-7713
AD  - Institute of Cytology of the Russian Academy of Sciences, 194064 St. Petersburg, 
      Russia.
FAU - Lazarev, Vladimir F
AU  - Lazarev VF
AD  - Institute of Cytology of the Russian Academy of Sciences, 194064 St. Petersburg, 
      Russia.
LA  - eng
GR  - 18-74-10087/Russian Science Foundation/
GR  - 22-13-00298/Russian Science Foundation/
PT  - Journal Article
DEP - 20221220
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC9867013
OTO - NOTNLM
OT  - 3-(5-phenyl-1H-pyrrol-2-yl)quinoxalin-2(1H)-one
OT  - GAPDH
OT  - Hsp70
OT  - heat shock protein
OT  - hydrocortisone 21-hemisuccinate
OT  - rehabilitation therapy
OT  - secondary damage
OT  - small molecules
OT  - traumatic brain injury
COIS- The authors declare no conflict of interest.
EDAT- 2023/01/22 06:00
MHDA- 2023/01/22 06:01
PMCR- 2022/12/20
CRDT- 2023/01/21 01:49
PHST- 2022/11/09 00:00 [received]
PHST- 2022/12/12 00:00 [revised]
PHST- 2022/12/14 00:00 [accepted]
PHST- 2023/01/21 01:49 [entrez]
PHST- 2023/01/22 06:00 [pubmed]
PHST- 2023/01/22 06:01 [medline]
PHST- 2022/12/20 00:00 [pmc-release]
AID - pharmaceutics15010007 [pii]
AID - pharmaceutics-15-00007 [pii]
AID - 10.3390/pharmaceutics15010007 [doi]
PST - epublish
SO  - Pharmaceutics. 2022 Dec 20;15(1):7. doi: 10.3390/pharmaceutics15010007.