File Download

There are no files associated with this item.

Conference Paper: Kinesin-1 regulates extrasynaptic NMDAR targeting and its reduction can confer neuroprotection

TitleKinesin-1 regulates extrasynaptic NMDAR targeting and its reduction can confer neuroprotection
Authors
Issue Date2016
PublisherThe University of Hong Kong.
Citation
The 2016 Neuroscience Symposium and Annual Scientific Conference of the Hong Kong Society of Neurosciences, The University of Hong Kong, Hong Kong, 18 May 2016. In Programme Book, 2016, p. 26, abstract no. OP11 How to Cite?
AbstractThe cellular response to brain injury mediates the fate of the neuron. Previous studies to identify neuronal responses that could be protective indicated intracellular transport as a potential target, but the underlying mechanisms are still unknown. Here, we showed that a decreased level of kinesin-1, a microtubule-dependent molecular motor, confers neuroprotection by reducing extrasynaptic N-methyl-D-aspartate receptor (NMDAR) targeting and functioning. We found that kif5b, the heavy chain of kinesin-1, was down-regulated by ischemic preconditioning. A loss of 50% of Kif5b protected the neurons against excitotoxic insult and ischemia provoked neurodegeneration through the hypofunction of NMDARs. Kinesin-1 forms complex with NMDAR in vivo and the tail of Kif5b directly binds with the NR2B cytoplasmic tails. Decreased kinesin-1 reduces the formation of this complex in vivo, prevents NMDAR concentrating at extrasynaptic sites and inhibits calcium influx mediated by extrasynaptic NMDAR activation to confer neuroprotection. De novo upregulation of the reduced Kif5b level abolished such protection effects. Our findings reveal that kinesin-1 reduction benefits and protects the neurons against neurodegeneration by reducing the cellular response to NMDAR mediated excitotoxic insult, which is likely to be an intrinsic event in the early stage of neurodegeneration. This finding could lead to the development of therapeutic strategies that fine-tune the intracellular transport machinery to postpone or halt neurodegeneration.
DescriptionConference Theme: Nature and Nurture in Brain Functions
Persistent Identifierhttp://hdl.handle.net/10722/231492

 

DC FieldValueLanguage
dc.contributor.authorLin, R-
dc.contributor.authorDuan, Z-
dc.contributor.authorFung, ML-
dc.contributor.authorWang, J-
dc.contributor.authorNi, Y-
dc.contributor.authorWu, W-
dc.contributor.authorChan, YS-
dc.contributor.authorHuang, J-
dc.date.accessioned2016-09-20T05:23:31Z-
dc.date.available2016-09-20T05:23:31Z-
dc.date.issued2016-
dc.identifier.citationThe 2016 Neuroscience Symposium and Annual Scientific Conference of the Hong Kong Society of Neurosciences, The University of Hong Kong, Hong Kong, 18 May 2016. In Programme Book, 2016, p. 26, abstract no. OP11-
dc.identifier.urihttp://hdl.handle.net/10722/231492-
dc.descriptionConference Theme: Nature and Nurture in Brain Functions-
dc.description.abstractThe cellular response to brain injury mediates the fate of the neuron. Previous studies to identify neuronal responses that could be protective indicated intracellular transport as a potential target, but the underlying mechanisms are still unknown. Here, we showed that a decreased level of kinesin-1, a microtubule-dependent molecular motor, confers neuroprotection by reducing extrasynaptic N-methyl-D-aspartate receptor (NMDAR) targeting and functioning. We found that kif5b, the heavy chain of kinesin-1, was down-regulated by ischemic preconditioning. A loss of 50% of Kif5b protected the neurons against excitotoxic insult and ischemia provoked neurodegeneration through the hypofunction of NMDARs. Kinesin-1 forms complex with NMDAR in vivo and the tail of Kif5b directly binds with the NR2B cytoplasmic tails. Decreased kinesin-1 reduces the formation of this complex in vivo, prevents NMDAR concentrating at extrasynaptic sites and inhibits calcium influx mediated by extrasynaptic NMDAR activation to confer neuroprotection. De novo upregulation of the reduced Kif5b level abolished such protection effects. Our findings reveal that kinesin-1 reduction benefits and protects the neurons against neurodegeneration by reducing the cellular response to NMDAR mediated excitotoxic insult, which is likely to be an intrinsic event in the early stage of neurodegeneration. This finding could lead to the development of therapeutic strategies that fine-tune the intracellular transport machinery to postpone or halt neurodegeneration.-
dc.languageeng-
dc.publisherThe University of Hong Kong.-
dc.relation.ispartofNeuroscience 2016-
dc.titleKinesin-1 regulates extrasynaptic NMDAR targeting and its reduction can confer neuroprotection-
dc.typeConference_Paper-
dc.identifier.emailLin, R: linrzh@hku.hk-
dc.identifier.emailFung, ML: fungml@hku.hk-
dc.identifier.emailNi, Y: yanxiang@hkucc.hku.hk-
dc.identifier.emailWu, W: wtwu@hkucc.hku.hk-
dc.identifier.emailChan, YS: yschan@hku.hk-
dc.identifier.emailHuang, J: jdhuang@hku.hk-
dc.identifier.authorityFung, ML=rp00433-
dc.identifier.authorityWu, W=rp00419-
dc.identifier.authorityChan, YS=rp00318-
dc.identifier.authorityHuang, J=rp00451-
dc.identifier.hkuros266186-
dc.identifier.spage26, abstract no. OP11-
dc.identifier.epage26, abstract no. OP11-
dc.publisher.placeHong Kong-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats