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dc.contributor.author
Daneri Becerra, Cristina del Rosario
dc.contributor.author
Patiño Gaillez, Michelle Geraldine Sissel
dc.contributor.author
Galigniana, Mario Daniel
dc.date.available
2021-06-02T01:48:57Z
dc.date.issued
2020-12
dc.identifier.citation
Daneri Becerra, Cristina del Rosario; Patiño Gaillez, Michelle Geraldine Sissel; Galigniana, Mario Daniel; Proof that the high molecular weight immunophilin FKBP52 mediates the in vivo neuroregenerative effect of the macrolide FK506; Pergamon-Elsevier Science Ltd; Biochemical Pharmacology; 182; 12-2020; 1-10
dc.identifier.issn
0006-2952
dc.identifier.uri
http://hdl.handle.net/11336/132948
dc.description.abstract
The immunosuppressant drug FK506 (or tacrolimus) is a macrolide that binds selectively to immunophilins belonging to the FK506-binding protein (FKBP) subfamily, which are abundantly expressed proteins in neurons of the peripheral and central nervous systems. Interestingly, it has been reported that FK506 increases neurite outgrowth in cell cultures, implying a potential impact in putative treatments of neurodegenerative disorders and injuries of the nervous system. Nonetheless, the mechanism of action of this compound is poorly understood and remains to be elucidated, with the only certainty that its neurotrophic effect is independent of its primary immunosuppressant activity. In this study it is demonstrated that FK506 shows efficient neurotrophic action in vitro and profound effects on the recovery of locomotor activity, behavioural features, and erectile function of mice that underwent surgical spinal cord injury. The recovery of the locomotor activity was studied in knock-out mice for either immunophilin, FKBP51 or FKBP52. The experimental evidence demonstrates that the neurotrophic actions of FK506 are the consequence of its binding to FKBP52, whereas FK506 interaction with the close-related partner immunophilin FKBP51 antagonises the function of FKBP52. Importantly, our study also demonstrates that other immunophilins do not replace FKBP52. It is concluded that the final biological response is the resulting outcome of the drug binding to both immunophilins, FKBP51 and FKBP52, the latter being the one that commands the dominant neurotrophic action in vivo.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Pergamon-Elsevier Science Ltd
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
FKBP51
dc.subject
FKBP52
dc.subject
IMMUNOPHILINS
dc.subject
NEUROREGENERATION
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SPINAL CORD INJURY
dc.subject
TACROLIMUS
dc.subject.classification
Bioquímica y Biología Molecular
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Proof that the high molecular weight immunophilin FKBP52 mediates the in vivo neuroregenerative effect of the macrolide FK506
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2021-04-22T20:06:43Z
dc.journal.volume
182
dc.journal.pagination
1-10
dc.journal.pais
Países Bajos
dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Daneri Becerra, Cristina del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.description.fil
Fil: Patiño Gaillez, Michelle Geraldine Sissel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.description.fil
Fil: Galigniana, Mario Daniel. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
dc.journal.title
Biochemical Pharmacology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.bcp.2020.114204
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/purl/https://www.sciencedirect.com/science/article/abs/pii/S0006295220304408?via%3Dihub
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