Use this url to cite publication: https://hdl.handle.net/20.500.12512/112384
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TLR4 Receptors and Caspase-1 Mediate Extracellular Tau-Induced Neurotoxicity in Neuronal-Glial Co-Cultures / Katryna Pampuscenko, Ramune Morkuniene, Vilmante Borutaite
Type of publication
Tezės kitame recenzuojamame leidinyje / Theses in other peer-reviewed publication (T1e)
Title
TLR4 Receptors and Caspase-1 Mediate Extracellular Tau-Induced Neurotoxicity in Neuronal-Glial Co-Cultures / Katryna Pampuscenko, Ramune Morkuniene, Vilmante Borutaite
Publisher (trusted)
Vilnius University Press |
Date Issued
Date Issued |
---|
2021-11-26 |
Extent
p. 45-45.
Is part of
XIII International Conference of the Lithuanian Neuroscience Association „CONSCIOUSNESS“ (LNA conference) : 26 November 2021, Kaunas, Lithuania : Virtual Conference : Abstract book / Vilnius University. Lithuanian University of Health Sciences. Vytautas Magnus University. Vilnius : Vilnius University Press, 2021. ISBN 9786090706794.
Version
Originalus / Original
Description
no. 22
Poster presentations
ISBN 978-609-07-0679-4 (digital PDF)
Field of Science
Abstract
Introduction. Tauopathies are a group of neurodegenerative diseases which development is closely associated with pathological changes of tubulin-associated unit (tau) protein. Intracellular tau aggregates are considered to be a major feature of tauopathies, but extracellular tau found in cerebrospinal fluid also rises with disease progression. Increasing evidence suggests that tau pathology spreads within anatomically connected brain regions and that intact neurons can secrete and take up exogenous tau protein which in turn induces fibrillization of intracellular tau in prion-like manner. Recently, intra- and extracellular tau protein was demonstrated to directly activate microglial cells via NLRP3–ASC inflammasome which catalyses caspase-1 formation. We have previously shown that extracellular tau2N4R induces phagocytosis of viable neurons by activated microglia and in this study, we aimed to investigate whether caspase-1 and Toll-like 4 (TLR4) receptors mediating NLRP3–ASC/ caspase-1 pathway activation are involved in tau2N4R -induced neuronal loss. Methods. Primary neuron-glial cell co-cultures from rat (Wistar) cerebellum were treated with recombinant tau2N4R protein with or without pre-incubation with YVAD-CHO, VX- 765 and anti-TLR4 antibody. Fluorescence and confocal microscopy were used to determine neuronal clearance signal transmission: cell viability was assessed by Hoeschst33342/ propidium iodide staining, microglial cells were labelled with isolectin IB4-AlexaFluor488, caspase-1 activation was evaluated using FamFlica kit. Results. Our results show that loss of neurons and microglial proliferation induced by tau2N4R protein in primary neuronal-glial co-cultures were completely prevented by caspase- 1 inhibitors YVAD-CHO and VX-765. After treatment with tau2N4R active caspase-1 labelled by FamFlica localized within microglial cells, but not neurons. We also found that blockage of TLR4 receptors by antibody prevented caspase-1 activation[...].
Type of document
type::text::conference output::conference proceedings::conference paper
ISBN (of the container)
9786090706794
Other Identifier(s)
(LSMU ALMA)990001049610107106
Coverage Spatial
Lietuva / Lithuania (LT)
Language
Anglų / English (en)