Cited 151 times in
Novel osmotin inhibits SREBP2 via the AdipoR1/AMPK/SIRT1 pathway to improve Alzheimer's disease neuropathological deficits
DC Field | Value | Language |
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dc.contributor.author | 정승수 | - |
dc.date.accessioned | 2017-11-02T08:15:22Z | - |
dc.date.available | 2017-11-02T08:15:22Z | - |
dc.date.issued | 2017 | - |
dc.identifier.issn | 1359-4184 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/154258 | - |
dc.description.abstract | Extensive evidence has indicated that a high rate of cholesterol biogenesis and abnormal neuronal energy metabolism play key roles in Alzheimer's disease (AD) pathogenesis. Here, for we believe the first time, we used osmotin, a plant protein homolog of mammalian adiponectin, to determine its therapeutic efficacy in different AD models. Our results reveal that osmotin treatment modulated adiponectin receptor 1 (AdipoR1), significantly induced AMP-activated protein kinase (AMPK)/Sirtuin 1 (SIRT1) activation and reduced SREBP2 (sterol regulatory element-binding protein 2) expression in both in vitro and in vivo AD models and in Adipo-/- mice. Via the AdipoR1/AMPK/SIRT1/SREBP2 signaling pathway, osmotin significantly diminished amyloidogenic Aβ production, abundance and aggregation, accompanied by improved pre- and post-synaptic dysfunction, cognitive impairment, memory deficits and, most importantly, reversed the suppression of long-term potentiation in AD mice. Interestingly, AdipoR1, AMPK and SIRT1 silencing not only abolished osmotin capability but also further enhanced AD pathology by increasing SREBP2, amyloid precursor protein (APP) and β-secretase (BACE1) expression and the levels of toxic Aβ production. However, the opposite was true for SREBP2 when silenced using small interfering RNA in APPswe/ind-transfected SH-SY5Y cells. Similarly, osmotin treatment also enhanced the non-amyloidogenic pathway by activating the α-secretase gene that is, ADAM10, in an AMPK/SIRT1-dependent manner. These results suggest that osmotin or osmotin-based therapeutic agents might be potential candidates for AD treatment. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Nature Publishing Group Specialist Journals | - |
dc.relation.isPartOf | MOLECULAR PSYCHIATRY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | AMP-Activated Protein Kinases/drug effects | - |
dc.subject.MESH | Alzheimer Disease/drug therapy | - |
dc.subject.MESH | Alzheimer Disease/genetics | - |
dc.subject.MESH | Alzheimer Disease/metabolism | - |
dc.subject.MESH | Amyloid Precursor Protein Secretases/metabolism | - |
dc.subject.MESH | Amyloid beta-Peptides/metabolism | - |
dc.subject.MESH | Amyloid beta-Protein Precursor/genetics | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Disease Models, Animal | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Long-Term Potentiation/physiology | - |
dc.subject.MESH | Memory Disorders/genetics | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Transgenic | - |
dc.subject.MESH | Phosphorylation | - |
dc.subject.MESH | Plant Proteins/pharmacology | - |
dc.subject.MESH | Plant Proteins/physiology | - |
dc.subject.MESH | Plant Proteins/therapeutic use* | - |
dc.subject.MESH | Receptors, Adiponectin/drug effects | - |
dc.subject.MESH | Receptors, Adiponectin/metabolism | - |
dc.subject.MESH | Signal Transduction/genetics | - |
dc.subject.MESH | Sirtuin 1/drug effects | - |
dc.subject.MESH | Sterol Regulatory Element Binding Protein 2/antagonists & inhibitors* | - |
dc.subject.MESH | Sterol Regulatory Element Binding Protein 2/drug effects | - |
dc.subject.MESH | Sterol Regulatory Element Binding Protein 2/metabolism* | - |
dc.title | Novel osmotin inhibits SREBP2 via the AdipoR1/AMPK/SIRT1 pathway to improve Alzheimer's disease neuropathological deficits | - |
dc.type | Article | - |
dc.publisher.location | England | - |
dc.contributor.college | College of Medicine | - |
dc.contributor.department | Dept. of Physiology | - |
dc.contributor.googleauthor | S A Shah | - |
dc.contributor.googleauthor | G H Yoon | - |
dc.contributor.googleauthor | S S Chung | - |
dc.contributor.googleauthor | M N Abid | - |
dc.contributor.googleauthor | T H Kim | - |
dc.contributor.googleauthor | H Y Lee | - |
dc.contributor.googleauthor | M O Kim | - |
dc.identifier.doi | 10.1038/mp.2016.23 | - |
dc.contributor.localId | A03643 | - |
dc.relation.journalcode | J02269 | - |
dc.identifier.eissn | 1476-5578 | - |
dc.identifier.pmid | 27001618 | - |
dc.contributor.alternativeName | Chung, Seung Soo | - |
dc.contributor.affiliatedAuthor | Chung, Seung Soo | - |
dc.citation.title | Molecular Psychiatry | - |
dc.citation.volume | 22 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 407 | - |
dc.citation.endPage | 416 | - |
dc.identifier.bibliographicCitation | MOLECULAR PSYCHIATRY, Vol.22(3) : 407-416, 2017 | - |
dc.date.modified | 2017-11-01 | - |
dc.identifier.rimsid | 42227 | - |
dc.type.rims | ART | - |
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