Nec‐1 alleviates cognitive impairment with reduction of Aβ and tau abnormalities in APP/PS1 mice
Abstract Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive symptoms of learning and memory deficits. Such cognitive impairments are attributed to brain atrophy resulting from progressive neuronal and synaptic loss; therefore, alleviation of neural cell death is...
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| Format: | Article |
| Language: | English |
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Springer Nature
2017-01-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.201606566 |
| _version_ | 1797279846392397824 |
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| author | Seung‐Hoon Yang Dongkeun Kenneth Lee Jisu Shin Sejin Lee Seungyeop Baek Jiyoon Kim Hoyong Jung Jung‐Mi Hah YoungSoo Kim |
| author_facet | Seung‐Hoon Yang Dongkeun Kenneth Lee Jisu Shin Sejin Lee Seungyeop Baek Jiyoon Kim Hoyong Jung Jung‐Mi Hah YoungSoo Kim |
| author_sort | Seung‐Hoon Yang |
| collection | DOAJ |
| description | Abstract Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive symptoms of learning and memory deficits. Such cognitive impairments are attributed to brain atrophy resulting from progressive neuronal and synaptic loss; therefore, alleviation of neural cell death is as an important target of treatment as other classical hallmarks of AD, such as aggregation of amyloid‐β (Aβ) and hyperphosphorylation of tau. Here, we found that an anti‐necroptotic molecule necrostatin‐1 (Nec‐1) directly targets Aβ and tau proteins, alleviates brain cell death and ameliorates cognitive impairment in AD models. In the cortex and hippocampus of APP/PS1 double‐transgenic mice, Nec‐1 treatment reduced the levels of Aβ oligomers, plaques and hyperphosphorylated tau without affecting production of Aβ, while it altered the levels of apoptotic marker proteins. Our results showing multiple beneficial modes of action of Nec‐1 against AD provide evidence that Nec‐1 may serve an important role in the development of preventive approach for AD. |
| first_indexed | 2024-03-07T16:31:52Z |
| format | Article |
| id | doaj.art-b4bfa699b862455b8bffa2240606c5d6 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T16:31:52Z |
| publishDate | 2017-01-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-b4bfa699b862455b8bffa2240606c5d62024-03-03T10:20:06ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842017-01-0191617710.15252/emmm.201606566Nec‐1 alleviates cognitive impairment with reduction of Aβ and tau abnormalities in APP/PS1 miceSeung‐Hoon Yang0Dongkeun Kenneth Lee1Jisu Shin2Sejin Lee3Seungyeop Baek4Jiyoon Kim5Hoyong Jung6Jung‐Mi Hah7YoungSoo Kim8Convergence Research Center for Dementia and Center for Neuro‐Medicine Brain Science Institute Korea Institute of Science and Technology Seoul KoreaConvergence Research Center for Dementia and Center for Neuro‐Medicine Brain Science Institute Korea Institute of Science and Technology Seoul KoreaConvergence Research Center for Dementia and Center for Neuro‐Medicine Brain Science Institute Korea Institute of Science and Technology Seoul KoreaConvergence Research Center for Dementia and Center for Neuro‐Medicine Brain Science Institute Korea Institute of Science and Technology Seoul KoreaConvergence Research Center for Dementia and Center for Neuro‐Medicine Brain Science Institute Korea Institute of Science and Technology Seoul KoreaConvergence Research Center for Dementia and Center for Neuro‐Medicine Brain Science Institute Korea Institute of Science and Technology Seoul KoreaDepartment of Pharmacy College of Pharmacy & Institute of Pharmaceutical Science and Technology Hanyang University Ansan Kyeonggi‐do KoreaDepartment of Pharmacy College of Pharmacy & Institute of Pharmaceutical Science and Technology Hanyang University Ansan Kyeonggi‐do KoreaConvergence Research Center for Dementia and Center for Neuro‐Medicine Brain Science Institute Korea Institute of Science and Technology Seoul KoreaAbstract Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive symptoms of learning and memory deficits. Such cognitive impairments are attributed to brain atrophy resulting from progressive neuronal and synaptic loss; therefore, alleviation of neural cell death is as an important target of treatment as other classical hallmarks of AD, such as aggregation of amyloid‐β (Aβ) and hyperphosphorylation of tau. Here, we found that an anti‐necroptotic molecule necrostatin‐1 (Nec‐1) directly targets Aβ and tau proteins, alleviates brain cell death and ameliorates cognitive impairment in AD models. In the cortex and hippocampus of APP/PS1 double‐transgenic mice, Nec‐1 treatment reduced the levels of Aβ oligomers, plaques and hyperphosphorylated tau without affecting production of Aβ, while it altered the levels of apoptotic marker proteins. Our results showing multiple beneficial modes of action of Nec‐1 against AD provide evidence that Nec‐1 may serve an important role in the development of preventive approach for AD.https://doi.org/10.15252/emmm.201606566Alzheimer's diseaseAβ aggregationcognitive deficitnecrostatin‐1tau hyperphosphorylation |
| spellingShingle | Seung‐Hoon Yang Dongkeun Kenneth Lee Jisu Shin Sejin Lee Seungyeop Baek Jiyoon Kim Hoyong Jung Jung‐Mi Hah YoungSoo Kim Nec‐1 alleviates cognitive impairment with reduction of Aβ and tau abnormalities in APP/PS1 mice EMBO Molecular Medicine Alzheimer's disease Aβ aggregation cognitive deficit necrostatin‐1 tau hyperphosphorylation |
| title | Nec‐1 alleviates cognitive impairment with reduction of Aβ and tau abnormalities in APP/PS1 mice |
| title_full | Nec‐1 alleviates cognitive impairment with reduction of Aβ and tau abnormalities in APP/PS1 mice |
| title_fullStr | Nec‐1 alleviates cognitive impairment with reduction of Aβ and tau abnormalities in APP/PS1 mice |
| title_full_unstemmed | Nec‐1 alleviates cognitive impairment with reduction of Aβ and tau abnormalities in APP/PS1 mice |
| title_short | Nec‐1 alleviates cognitive impairment with reduction of Aβ and tau abnormalities in APP/PS1 mice |
| title_sort | nec 1 alleviates cognitive impairment with reduction of aβ and tau abnormalities in app ps1 mice |
| topic | Alzheimer's disease Aβ aggregation cognitive deficit necrostatin‐1 tau hyperphosphorylation |
| url | https://doi.org/10.15252/emmm.201606566 |
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