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001-es BibID:	BIBFORM100131
Első szerző:	Reddiar, Sanjeevini Babu
Cím:	Lipopolysaccharide influences the plasma and brain pharmacokinetics of subcutaneously-administered HsTX1[R14A], a KV1.3-blocking peptide / Reddiar Sanjeevini Babu, Jin Liang, Wai Dorothy C. C., Csoti Agota, Panyi Gyorgy, Norton Raymond S., Nicolazzo Joseph A.
Dátum:	2021
ISSN:	0041-0101
Megjegyzések:	KV1.3 is a voltage-gated potassium channel that is upregulated in neuroinflammatory conditions, such as Alzheimer's disease and Parkinson's disease. HsTX1[R14A] is a potent and selective peptide blocker of KV1.3 with the potential to block microglial KV1.3, but its brain uptake is expected to be limited owing to the restrictive nature of the blood-brain barrier. To assess its peripheral and brain exposure, a LC-MS/MS assay was developed to quantify HsTX1[R14A] concentrations in mouse plasma and brain homogenate that was reliable and reproducible in the range of 6.7?66.7 nM (r2 = 0.9765) and 15?150 pmol/g (r2 = 0.9984), respectively. To assess if neuroinflammation affected HsTX1[R14A] disposition, C57BL/6 mice were administered HsTX1[R14A] subcutaneously (2 mg/kg) 24 h after an intraperitoneal dose of Escherichia coli lipopolysaccharide (LPS), which is commonly used to induce neuroinflammation; brain and plasma concentrations of HsTX1[R14A] were then quantified over 120 min. LPS treatment significantly retarded the decline in HsTX1[R14A] plasma concentrations, presumably as a result of reducing renal clearance, and led to substantial brain uptake of HsTX1[R14A], presumably through disruption of brain inter-endothelial tight junctions. This study suggests that HsTX1[R14A] may reach microglia in sufficient concentrations to block KV1.3 in neuroinflammatory conditions, and therefore has the potential to reduce neurodegenerative diseases.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Toxicon. - 195 (2021), p. 29-36. -
További szerzők:	Jin, Liang Wai, Dorothy C. C. Csóti Ágota (1989-) (biológus) Panyi György (1966-) (biofizikus) Norton, Raymond S. Nicolazzo, Joseph A.
Pályázati támogatás:	K119417 OTKA EFOP-3.6.1-16-2016-00022 EFOP GINOP-2.3.2-15-2016-00015 GINOP
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