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The Role of Green Tea Catechin Epigallocatechin Gallate (EGCG) and Mammalian Target of Rapamycin (mTOR) Inhibitor PP242 (Torkinib) in the Treatment of Spinal Cord Injury
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SYSNO ASEP 0580306 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title The Role of Green Tea Catechin Epigallocatechin Gallate (EGCG) and Mammalian Target of Rapamycin (mTOR) Inhibitor PP242 (Torkinib) in the Treatment of Spinal Cord Injury Author(s) Machová-Urdzíková, Lucia (UEM-P) ORCID
Cimermanová, Veronika (UEM-P) ORCID
Kárová, Kristýna (UEM-P) RID
Dominguez, J. (US)
Štěpánková, Kateřina (UEM-P) ORCID
Petrovičová, Michaela (UEM-P)
Havelíková, Kateřina (UEM-P)
Gandhi, Ch.D. (US)
Jhanwar-Uniyal, M. (US)
Jendelová, Pavla (UEM-P) RID, ORCIDArticle number 363 Source Title Antioxidants. - : MDPI
Roč. 12, č. 2 (2023)Number of pages 17 s. Language eng - English Country CH - Switzerland Keywords spinal cord injury ; mTOR pathway ; EGCG ; PP 242 ; inflammatory response ; neuroregeneration ; astrogliosis ; axonal growth OECD category Neurosciences (including psychophysiology R&D Projects LTAUSA17120 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LQ1604 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) EF15_003/0000419 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) LM2015064 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UEM-P - RVO:68378041 UT WOS 000938274600001 EID SCOPUS 85149255332 DOI 10.3390/antiox12020363 Annotation Spinal cord injury (SCI) is a devastating condition that has physical and psychological consequences for patients. SCI is accompanied by scar formation and systemic inflammatory response leading to an intense degree of functional loss. The catechin, epigallocatechin gallate (EGCG), an active compound found in green tea, holds neuroprotective features and is known for its anti-inflammatory potential. The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that exists in two functionally distinct complexes termed mTOR complex 1 and 2 (mTORC1, mTORC2). Inhibition of mTORC1 by rapamycin causes neuroprotection, leading to partial recovery from SCI. In this study the effects of EGCG, PP242 (an inhibitor of both complexes of mTOR), and a combination of EGCG and PP242 in SCI have been examined. It has been found that both EGCG and PP242 significantly improved sensory/motor functions following SCI. However, EGCG appeared to be more effective (BBB motor test, from 2 to 8 weeks after SCI, p = 0.019, p = 0.007, p = 0.006, p = 0.006, p = 0.05, p = 0.006, and p = 0.003, respectively). The only exception was the Von Frey test, where EGCG was ineffective, while mTOR inhibition by PP242, as well as PP242 in combination with EGCG, significantly reduced withdrawal latency starting from week three (combinatorial therapy (EGCG + PP242) vs. control at 3, 5, and 7 weeks, p = 0.011, p = 0.007, and p = 0.05, respectively). It has been found that EGCG was as effective as PP242 in suppressing mTOR signaling pathways, as evidenced by a reduction in phosphorylated S6 expression (PP242 (t-test, p < 0.0001) or EGCG (t-test, p = 0.0002)). These results demonstrate that EGCG and PP242 effectively suppress mTOR pathways, resulting in recovery from SCI in rats, and that EGCG acts via suppressing mTOR pathways. Workplace Institute of Experimental Medicine Contact Lenka Koželská, lenka.kozelska@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Year of Publishing 2024 Electronic address https://www.mdpi.com/2076-3921/12/2/363
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