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Nec-1 alleviates cognitive impairment with reduction of Aβ and tau abnormalities in APP/PS1 mice.
| Content Provider | Europe PMC |
|---|---|
| Author | Yang, Seung‐Hoon Lee, Dongkeun Kenneth Shin, Jisu Lee, Sejin Baek, Seungyeop Kim, Jiyoon Jung, Hoyong Hah, Jung‐Mi Kim, YoungSoo |
| 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. |
| Page Count | 17 |
| ISSN | 17574676 |
| Journal | EMBO Molecular Medicine |
| Volume Number | 9 |
| PubMed Central reference number | PMC5210088 |
| Issue Number | 1 |
| PubMed reference number | 27861127 |
| e-ISSN | 17574684 |
| DOI | 10.15252/emmm.201606566 |
| Language | English |
| Publisher | John Wiley and Sons Inc. |
| Publisher Date | 2017-01-01 |
| Publisher Place | Hoboken |
| Access Restriction | Open |
| Rights License | This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2016 The Authors. Published under the terms of the CC BY 4.0 license |
| Subject Keyword | Alzheimer's disease Aβ aggregation cognitive deficit necrostatin‐1 tau hyperphosphorylation Neuroscience Pharmacology & Drug Discovery |
| Content Type | Text |
| Resource Type | Article |
| Subject | Molecular Medicine |
