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PubMed: 29540553

Title
SIRT1 Deacetylates Tau and Reduces Pathogenic Tau Spread in a Mouse Model of Tauopathy.
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Volume
38
Issue
None
Pages
3680-3688
Date
2018-04-11
Authors
Devidze N | Gan L | Gestwicki JE | Johnson JR | Krogan NJ | Li Y | Masliah E | Min SW | Mok SA | Sohn PD

Evidence 0bd4e49285
JSON

Here we show that the protein deacetylase SIRT1 reduces tau acetylation in a mouse model of neurodegeneration. SIRT1 deficiency in the brain aggravates synapse loss and behavioral disinhibition, and SIRT1 overexpression ameliorates propagation of tau pathology.

a(GO:"neuron to neuron synapse") positiveCorrelation p(MGI:Sirt1) View Subject | View Object

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p(MGI:Sirt1) decreases p(MGI:Mapt, pmod(Ac, Lys, 174)) View Subject | View Object

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p(MGI:Sirt1) positiveCorrelation a(GO:"neuron to neuron synapse") View Subject | View Object

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p(MGI:Sirt1) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

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path(MESH:"Alzheimer Disease") negativeCorrelation p(MGI:Sirt1) View Subject | View Object

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Evidence 323a2e86e7
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SIRT1 deficiency exacerbates premature mortality, synapse loss, and behavioral disinhibition in tauP301S TG mice of both sexes. SIRT1 overexpression into the hippocampus reduces acetylated K174 tau and significantly attenuates the spread of tau pathology into anatomically connected brain regions of tauP301S transgenic mice of both sexes.

a(HBP:"Pathological Tau Spreading") negativeCorrelation act(p(HGNC:SIRT1)) View Subject | View Object

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Annotations
Uberon
hippocampal formation

p(HGNC:MAPT, pmod(Ac, Lys, 174)) negativeCorrelation act(p(HGNC:SIRT1)) View Subject | View Object

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Annotations
Uberon
hippocampal formation

act(p(HGNC:SIRT1)) negativeCorrelation p(HGNC:MAPT, pmod(Ac, Lys, 174)) View Subject | View Object

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Annotations
Uberon
hippocampal formation

act(p(HGNC:SIRT1)) negativeCorrelation a(HBP:"Pathological Tau Spreading") View Subject | View Object

Appears in Networks:
Annotations
Uberon
hippocampal formation

Evidence f6b2da4508
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SIRT1 activation or elevation ameliorates pathology and neurodegeneration in AD (Qin et al., 2006; Kim et al., 2007). Loss of SIRT1 induces impairment of learning and memory (Gao et al., 2010; Michán et al., 2010).

bp(GO:learning) positiveCorrelation p(HGNC:SIRT1) View Subject | View Object

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bp(GO:memory) positiveCorrelation p(HGNC:SIRT1) View Subject | View Object

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act(p(HGNC:SIRT1)) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

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p(HGNC:SIRT1) positiveCorrelation bp(GO:learning) View Subject | View Object

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p(HGNC:SIRT1) positiveCorrelation bp(GO:memory) View Subject | View Object

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path(MESH:"Alzheimer Disease") negativeCorrelation act(p(HGNC:SIRT1)) View Subject | View Object

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Evidence 6311551b5e
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After pretreating hTau neurons with oligo Aβ-42 (1000 ng/ml), Sirt3 levels were reduced (Fig. 6b and e). This reduction in Sirt3 was translated into an increase in total tau and Ac-tau.

p(HGNC:MAPT) negativeCorrelation p(MGI:Sirt3) View Subject | View Object

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p(HGNC:APP, frag("672_713")) negativeCorrelation p(MGI:Sirt3) View Subject | View Object

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p(HGNC:MAPT, pmod(Ac)) negativeCorrelation p(MGI:Sirt3) View Subject | View Object

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p(MGI:Sirt3) negativeCorrelation p(HGNC:APP, frag("672_713")) View Subject | View Object

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p(MGI:Sirt3) negativeCorrelation p(HGNC:MAPT) View Subject | View Object

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p(MGI:Sirt3) negativeCorrelation p(HGNC:MAPT, pmod(Ac)) View Subject | View Object

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Evidence 1de677a5c4
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Sirt3 levels were reduced in the entorhinal cortex, the middle temporal gyrus, and the superior frontal gyrus of AD subjects compared to those of CN and was associated with poorer test scores of neuropsychological evaluation and the severity of tau pathology.

p(MGI:Sirt3) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

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Annotations
Uberon
entorhinal cortex
Uberon
middle temporal gyrus
Uberon
superior frontal gyrus

path(MESH:"Alzheimer Disease") negativeCorrelation p(MGI:Sirt3) View Subject | View Object

Appears in Networks:
Annotations
Uberon
entorhinal cortex
Uberon
middle temporal gyrus
Uberon
superior frontal gyrus

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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.