Dysregulation of the mTOR pathway mediates impairment of synaptic plasticity in a mouse model of Alzheimer's disease.
The mammalian target of rapamycin (mTOR) is an evolutionarily conserved Ser/Thr protein kinase that plays a pivotal role in multiple fundamental biological processes, including synaptic plasticity. We explored the relationship between the mTOR pathway and β-amyloid (Aβ)-induced synaptic dysfunction,...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2010-09-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2942840?pdf=render |
| _version_ | 1819278554007863296 |
|---|---|
| author | Tao Ma Charles A Hoeffer Estibaliz Capetillo-Zarate Fangmin Yu Helen Wong Michael T Lin Davide Tampellini Eric Klann Robert D Blitzer Gunnar K Gouras |
| author_facet | Tao Ma Charles A Hoeffer Estibaliz Capetillo-Zarate Fangmin Yu Helen Wong Michael T Lin Davide Tampellini Eric Klann Robert D Blitzer Gunnar K Gouras |
| author_sort | Tao Ma |
| collection | DOAJ |
| description | The mammalian target of rapamycin (mTOR) is an evolutionarily conserved Ser/Thr protein kinase that plays a pivotal role in multiple fundamental biological processes, including synaptic plasticity. We explored the relationship between the mTOR pathway and β-amyloid (Aβ)-induced synaptic dysfunction, which is considered to be critical in the pathogenesis of Alzheimer's disease (AD).We provide evidence that inhibition of mTOR signaling correlates with impairment in synaptic plasticity in hippocampal slices from an AD mouse model and in wild-type slices exposed to exogenous Aβ1-42. Importantly, by up-regulating mTOR signaling, glycogen synthase kinase 3 (GSK3) inhibitors rescued LTP in the AD mouse model, and genetic deletion of FK506-binding protein 12 (FKBP12) prevented Aβ-induced impairment in long-term potentiation (LTP). In addition, confocal microscopy demonstrated co-localization of intraneuronal Aβ42 with mTOR.These data support the notion that the mTOR pathway modulates Aβ-related synaptic dysfunction in AD. |
| first_indexed | 2024-12-24T00:13:51Z |
| format | Article |
| id | doaj.art-7bb58ed8478441b6814903076fbbea7a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-24T00:13:51Z |
| publishDate | 2010-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7bb58ed8478441b6814903076fbbea7a2022-12-21T17:24:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-09-015910.1371/journal.pone.0012845Dysregulation of the mTOR pathway mediates impairment of synaptic plasticity in a mouse model of Alzheimer's disease.Tao MaCharles A HoefferEstibaliz Capetillo-ZarateFangmin YuHelen WongMichael T LinDavide TampelliniEric KlannRobert D BlitzerGunnar K GourasThe mammalian target of rapamycin (mTOR) is an evolutionarily conserved Ser/Thr protein kinase that plays a pivotal role in multiple fundamental biological processes, including synaptic plasticity. We explored the relationship between the mTOR pathway and β-amyloid (Aβ)-induced synaptic dysfunction, which is considered to be critical in the pathogenesis of Alzheimer's disease (AD).We provide evidence that inhibition of mTOR signaling correlates with impairment in synaptic plasticity in hippocampal slices from an AD mouse model and in wild-type slices exposed to exogenous Aβ1-42. Importantly, by up-regulating mTOR signaling, glycogen synthase kinase 3 (GSK3) inhibitors rescued LTP in the AD mouse model, and genetic deletion of FK506-binding protein 12 (FKBP12) prevented Aβ-induced impairment in long-term potentiation (LTP). In addition, confocal microscopy demonstrated co-localization of intraneuronal Aβ42 with mTOR.These data support the notion that the mTOR pathway modulates Aβ-related synaptic dysfunction in AD.http://europepmc.org/articles/PMC2942840?pdf=render |
| spellingShingle | Tao Ma Charles A Hoeffer Estibaliz Capetillo-Zarate Fangmin Yu Helen Wong Michael T Lin Davide Tampellini Eric Klann Robert D Blitzer Gunnar K Gouras Dysregulation of the mTOR pathway mediates impairment of synaptic plasticity in a mouse model of Alzheimer's disease. PLoS ONE |
| title | Dysregulation of the mTOR pathway mediates impairment of synaptic plasticity in a mouse model of Alzheimer's disease. |
| title_full | Dysregulation of the mTOR pathway mediates impairment of synaptic plasticity in a mouse model of Alzheimer's disease. |
| title_fullStr | Dysregulation of the mTOR pathway mediates impairment of synaptic plasticity in a mouse model of Alzheimer's disease. |
| title_full_unstemmed | Dysregulation of the mTOR pathway mediates impairment of synaptic plasticity in a mouse model of Alzheimer's disease. |
| title_short | Dysregulation of the mTOR pathway mediates impairment of synaptic plasticity in a mouse model of Alzheimer's disease. |
| title_sort | dysregulation of the mtor pathway mediates impairment of synaptic plasticity in a mouse model of alzheimer s disease |
| url | http://europepmc.org/articles/PMC2942840?pdf=render |
| work_keys_str_mv | AT taoma dysregulationofthemtorpathwaymediatesimpairmentofsynapticplasticityinamousemodelofalzheimersdisease AT charlesahoeffer dysregulationofthemtorpathwaymediatesimpairmentofsynapticplasticityinamousemodelofalzheimersdisease AT estibalizcapetillozarate dysregulationofthemtorpathwaymediatesimpairmentofsynapticplasticityinamousemodelofalzheimersdisease AT fangminyu dysregulationofthemtorpathwaymediatesimpairmentofsynapticplasticityinamousemodelofalzheimersdisease AT helenwong dysregulationofthemtorpathwaymediatesimpairmentofsynapticplasticityinamousemodelofalzheimersdisease AT michaeltlin dysregulationofthemtorpathwaymediatesimpairmentofsynapticplasticityinamousemodelofalzheimersdisease AT davidetampellini dysregulationofthemtorpathwaymediatesimpairmentofsynapticplasticityinamousemodelofalzheimersdisease AT ericklann dysregulationofthemtorpathwaymediatesimpairmentofsynapticplasticityinamousemodelofalzheimersdisease AT robertdblitzer dysregulationofthemtorpathwaymediatesimpairmentofsynapticplasticityinamousemodelofalzheimersdisease AT gunnarkgouras dysregulationofthemtorpathwaymediatesimpairmentofsynapticplasticityinamousemodelofalzheimersdisease |