GSK-3β and Memory Formation
In Alzheimer’s disease (AD), tau hyperphosphorylation and neurofibrillary tangle (NFT) formation are strongly associated with dementia. Memory impairment is a characteristic, early symptom of AD. Glycogen synthase kinase 3 β (GSK-3β), which is activated in response to amyloid β (Aβ) formation,...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2012-04-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnmol.2012.00047/full |
| _version_ | 1818174198754836480 |
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| author | Akihiko eTakashima |
| author_facet | Akihiko eTakashima |
| author_sort | Akihiko eTakashima |
| collection | DOAJ |
| description | In Alzheimer’s disease (AD), tau hyperphosphorylation and neurofibrillary tangle (NFT) formation are strongly associated with dementia. Memory impairment is a characteristic, early symptom of AD. Glycogen synthase kinase 3 β (GSK-3β), which is activated in response to amyloid β (Aβ) formation, and the normal process of aging, hyperphosphorylates tau present in the NFTs. Furthermore, activation of GSK-3β inhibits synaptic long-term potentiation (LTP) through tau. It is therefore likely, that activation of GSK-3β is responsible for the memory problems seen in both advanced age, and AD. Indeed, inhibition of GSK-3 by lithium halts the progression of symptoms in patients with mild cognitive impairment (MCI). However, long-term treatment of lithium increases the risk of dementia in old age, in bipolar patients. To understand the role of GSK-3β in brain function, we analyzed memory formation in GSK-3β heterozygote, knockout mice. Results indicate that these mice show impaired memory reconsolidation. It would seem that activation of GSK-3β is required for memory maintenance, with a higher requirement as animals age, and the volume of memory increases. This in turn causes exaggerated activation of GSK-3β, leading to memory problems, and the formation of NFTs. |
| first_indexed | 2024-12-11T19:40:36Z |
| format | Article |
| id | doaj.art-2ba2b53ee155439b855248664d2797e1 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-11T19:40:36Z |
| publishDate | 2012-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-2ba2b53ee155439b855248664d2797e12022-12-22T00:53:02ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992012-04-01510.3389/fnmol.2012.0004716264GSK-3β and Memory FormationAkihiko eTakashima0National Center for Geriatrics and GerontologyIn Alzheimer’s disease (AD), tau hyperphosphorylation and neurofibrillary tangle (NFT) formation are strongly associated with dementia. Memory impairment is a characteristic, early symptom of AD. Glycogen synthase kinase 3 β (GSK-3β), which is activated in response to amyloid β (Aβ) formation, and the normal process of aging, hyperphosphorylates tau present in the NFTs. Furthermore, activation of GSK-3β inhibits synaptic long-term potentiation (LTP) through tau. It is therefore likely, that activation of GSK-3β is responsible for the memory problems seen in both advanced age, and AD. Indeed, inhibition of GSK-3 by lithium halts the progression of symptoms in patients with mild cognitive impairment (MCI). However, long-term treatment of lithium increases the risk of dementia in old age, in bipolar patients. To understand the role of GSK-3β in brain function, we analyzed memory formation in GSK-3β heterozygote, knockout mice. Results indicate that these mice show impaired memory reconsolidation. It would seem that activation of GSK-3β is required for memory maintenance, with a higher requirement as animals age, and the volume of memory increases. This in turn causes exaggerated activation of GSK-3β, leading to memory problems, and the formation of NFTs.http://journal.frontiersin.org/Journal/10.3389/fnmol.2012.00047/fullAgingAlzheimer's diseasetaumemory formationmemory impairment |
| spellingShingle | Akihiko eTakashima GSK-3β and Memory Formation Frontiers in Molecular Neuroscience Aging Alzheimer's disease tau memory formation memory impairment |
| title | GSK-3β and Memory Formation |
| title_full | GSK-3β and Memory Formation |
| title_fullStr | GSK-3β and Memory Formation |
| title_full_unstemmed | GSK-3β and Memory Formation |
| title_short | GSK-3β and Memory Formation |
| title_sort | gsk 3β and memory formation |
| topic | Aging Alzheimer's disease tau memory formation memory impairment |
| url | http://journal.frontiersin.org/Journal/10.3389/fnmol.2012.00047/full |
| work_keys_str_mv | AT akihikoetakashima gsk3bandmemoryformation |