2021
DOI: 10.3390/app11167673
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Doxycycline and Minocycline Act as Positive Allosteric Modulators of the PAC1 Receptor and Induce Plasminogen Activators in RT4 Schwann Cells

Abstract: Regeneration of peripheral nerves depends on the ability of axons to navigate through an altered extracellular environment. It has been suggested that Schwann cells facilitate this process through their secretion of neuropeptides and proteases. Using the RT4-D6P2T Schwann cell line (RT4), we have previously shown that RT4 cultures endogenously express the neuropeptide PACAP, and respond to exogenous stimulation by inducing the expression of tissue plasminogen activator (tPA) and urokinase plasminogen activator… Show more

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Cited by 5 publications
(3 citation statements)
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References 43 publications
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“…In a study by de Souza and collaborators, the authors describe these two peptides as neuroprotective and anti-inflammatory against experimental PD, acting mainly by reducing neuroinflammation, promoting dopaminergic neuronal survival and preserving cognitive functions [ 70 ]. Moreover, other evidence indicates that PACAP and BDNF [ 71 ] share similar neuroprotective pathways, as do VIP and ADNP [ 72 ]. Our results demonstrate these pathways are globally down-regulated in our rotenone model, suggesting that one of the modalities through which rotenone imparts damage to the CNS is via reducing the endogenous neuroprotective potential of these peptides.…”
Section: Discussionmentioning
confidence: 99%
“…In a study by de Souza and collaborators, the authors describe these two peptides as neuroprotective and anti-inflammatory against experimental PD, acting mainly by reducing neuroinflammation, promoting dopaminergic neuronal survival and preserving cognitive functions [ 70 ]. Moreover, other evidence indicates that PACAP and BDNF [ 71 ] share similar neuroprotective pathways, as do VIP and ADNP [ 72 ]. Our results demonstrate these pathways are globally down-regulated in our rotenone model, suggesting that one of the modalities through which rotenone imparts damage to the CNS is via reducing the endogenous neuroprotective potential of these peptides.…”
Section: Discussionmentioning
confidence: 99%
“…Protein was extracted using a radioimmunoprecipitation assay (RIPA) buffer containing protease inhibitors to preserve protein integrity (cOmplete, Mini, EDTA-free Protease Inhibitor Cocktail, Sigma-Aldrich, Castle Hill, NSW, Australia) as previously reported (Thomas Broome et al 2021b ). Protein quantification was determined using the bicinchoninic acid assay (Pierce BCA Protein Assay Kit, Thermo Fisher Scientific, VIC, Australia).…”
Section: Methodsmentioning
confidence: 99%
“…Their biological activities are mediated by three G protein-coupled receptors, namely, PAC1, VPAC1 and VPAC2 [ 19 , 20 ]. These two peptides, along with their high-affinity receptors, are generally referred to as the PACAP/VIP neuropeptide system [ 21 , 22 ]. This pleiotropic peptidergic system affords neuroprotection and immune modulation in several CNS and non-CNS regions [ 23 , 24 , 25 , 26 ], including the vascular compartment [ 27 , 28 ].…”
Section: Introductionmentioning
confidence: 99%