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p(HGNC:SIRT1)

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Entity

Name
SIRT1
Namespace
hgnc
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

Appears in Networks 5

Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing v1.0.0

Tau Modifications v1.9.5

Tau Modifications Sections of NESTOR

Oxidative stress in health and disease: The therapeutic potential of Nrf2 activation v1.0.0

Tau in physiology and pathology v1.0.0

Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells (NF-κB) - a Friend, a Foe, or a Bystander - in the Neurodegenerative Cascade and Pathogenesis of Alzheimer's Disease v1.0.0

In-Edges 15

a(CHEBI:"NAD(+)") increases act(p(HGNC:SIRT1)) View Subject | View Object

Because the class III deacetylase NAD- dependent protein deacetylase sirtuin 1 (SIRT1) requires nicotinamide adenine dinucleotide (NAD) to sustain its activity, this positive regulator of autophagy may also be considered a sensor 24 . PubMed:30116051

Appears in Networks:

a(CHEBI:"NAD(+)") increases act(p(HGNC:SIRT1)) View Subject | View Object

SIRT1 is activated by AMPK- mediated increases in nicotinamide, and it drives the ALN by inhibiting mTORC1, inducing FOXO1 and FOXO3 and activating key regulatory proteins such as ATG5, ATG7 and LC3. PubMed:30116051

Appears in Networks:

a(CHEBI:cilostazol) increases act(p(HGNC:SIRT1)) View Subject | View Object

Cilostazol (a phosphodiesterase 3 inhibitor) clears Aβ42 from neuronal cell lines by promoting autophagy, upregulating beclin 1, ATG5 and LC3, downregulating mTORC1 and inducing lysosomal cathepsin B; these actions of cilostazol involve activation of SIRT1 as well as upstream Tyr172 phosphorylation of AMPK 108,162,163 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Machado-Joseph Disease

bp(GO:aging) decreases act(p(HGNC:SIRT1)) View Subject | View Object

Activity of the deacetylase SIRT1 declines with age, partially owing to limited availability of its co fac- tor, nicotinamide 24,56,156 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Machado-Joseph Disease

act(p(FPLX:AMPK)) increases act(p(HGNC:SIRT1)) View Subject | View Object

Resveratrol can stimulate SIRT1 via AMPK (see above), and it also possesses an AMPK-independent mode of SIRT1 recruitment that participates in blunting the neurotoxicity of Aβ25–35 fragments in PC12 cells 160 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Machado-Joseph Disease

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

Second, while decr1eases in beclin 1 levels in AD remain to be confirmed, SIRT1 expression is diminished 24 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

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

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. PubMed:29540553

Appears in Networks:
Annotations
Uberon
hippocampal formation

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

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). PubMed:29540553

Appears in Networks:

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

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). PubMed:29540553

Appears in Networks:

p(HBP:"Tau epitope, AT8") negativeCorrelation act(p(HGNC:SIRT1)) View Subject | View Object

Thus, the increase in ac-tau induced by SIRT1 deficiency is accompanied by accumulation of pathogenic p-tau in primary neurons. In mouse brains, deleting SIRT1, which elevated ac-tau, also increased AT8-positive p-tau. PubMed:20869593

Appears in Networks:

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

Thus, the increase in ac-tau induced by SIRT1 deficiency is accompanied by accumulation of pathogenic p-tau in primary neurons. In mouse brains, deleting SIRT1, which elevated ac-tau, also increased AT8-positive p-tau. PubMed:20869593

Appears in Networks:

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

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. PubMed:29540553

Appears in Networks:
Annotations
Uberon
hippocampal formation

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

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). PubMed:29540553

Appears in Networks:

a(CHEBI:resveratrol) increases act(p(HGNC:SIRT1)) View Subject | View Object

The study also found that resveratrol, a putative activator of SIRT1 (Howitz et al., 2003), inhibited Nrf2-dependent transcription, apparently contradicting earlier reports that resveratrol activates Nrf2 (Chen et al., 2005; Ungvari et al., 2010). PubMed:22020111

Appears in Networks:

a(PUBCHEM:135316034) increases p(HGNC:SIRT1) View Subject | View Object

In our gene expression data, SIRT1 was induced 1.75-fold by Protandim (p = 0.015). PubMed:22020111

Appears in Networks:

Out-Edges 19

p(HGNC:SIRT1) increases bp(GO:macroautophagy) View Subject | View Object

Because the class III deacetylase NAD- dependent protein deacetylase sirtuin 1 (SIRT1) requires nicotinamide adenine dinucleotide (NAD) to sustain its activity, this positive regulator of autophagy may also be considered a sensor 24 . PubMed:30116051

Appears in Networks:

act(p(HGNC:SIRT1)) decreases act(p(FPLX:mTORC1)) View Subject | View Object

SIRT1 is activated by AMPK- mediated increases in nicotinamide, and it drives the ALN by inhibiting mTORC1, inducing FOXO1 and FOXO3 and activating key regulatory proteins such as ATG5, ATG7 and LC3. PubMed:30116051

Appears in Networks:

act(p(HGNC:SIRT1)) increases act(p(HGNC:FOXO1)) View Subject | View Object

SIRT1 is activated by AMPK- mediated increases in nicotinamide, and it drives the ALN by inhibiting mTORC1, inducing FOXO1 and FOXO3 and activating key regulatory proteins such as ATG5, ATG7 and LC3. PubMed:30116051

Appears in Networks:

act(p(HGNC:SIRT1)) increases act(p(HGNC:FOXO3)) View Subject | View Object

SIRT1 is activated by AMPK- mediated increases in nicotinamide, and it drives the ALN by inhibiting mTORC1, inducing FOXO1 and FOXO3 and activating key regulatory proteins such as ATG5, ATG7 and LC3. PubMed:30116051

Appears in Networks:

act(p(HGNC:SIRT1)) increases act(p(HGNC:ATG5)) View Subject | View Object

SIRT1 is activated by AMPK- mediated increases in nicotinamide, and it drives the ALN by inhibiting mTORC1, inducing FOXO1 and FOXO3 and activating key regulatory proteins such as ATG5, ATG7 and LC3. PubMed:30116051

Appears in Networks:

act(p(HGNC:SIRT1)) increases act(p(HGNC:ATG7)) View Subject | View Object

SIRT1 is activated by AMPK- mediated increases in nicotinamide, and it drives the ALN by inhibiting mTORC1, inducing FOXO1 and FOXO3 and activating key regulatory proteins such as ATG5, ATG7 and LC3. PubMed:30116051

Appears in Networks:

act(p(HGNC:SIRT1)) increases act(p(HGNC:MAP1LC3A)) View Subject | View Object

SIRT1 is activated by AMPK- mediated increases in nicotinamide, and it drives the ALN by inhibiting mTORC1, inducing FOXO1 and FOXO3 and activating key regulatory proteins such as ATG5, ATG7 and LC3. PubMed:30116051

Appears in Networks:

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

Thus, the increase in ac-tau induced by SIRT1 deficiency is accompanied by accumulation of pathogenic p-tau in primary neurons. In mouse brains, deleting SIRT1, which elevated ac-tau, also increased AT8-positive p-tau. PubMed:20869593

Appears in Networks:

act(p(HGNC:SIRT1)) negativeCorrelation p(HBP:"Tau epitope, AT8") View Subject | View Object

Thus, the increase in ac-tau induced by SIRT1 deficiency is accompanied by accumulation of pathogenic p-tau in primary neurons. In mouse brains, deleting SIRT1, which elevated ac-tau, also increased AT8-positive p-tau. PubMed:20869593

Appears in Networks:

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

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. PubMed:29540553

Appears in Networks:
Annotations
Uberon
hippocampal formation

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

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. PubMed:29540553

Appears in Networks:
Annotations
Uberon
hippocampal formation

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

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). PubMed:29540553

Appears in Networks:

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

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). PubMed:29540553

Appears in Networks:

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

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). PubMed:29540553

Appears in Networks:

act(p(HGNC:SIRT1)) directlyDecreases p(HGNC:SRSF2, pmod(Ac, Lys, 52)) View Subject | View Object

We found that SIRT1 interacts with and deacetylates SC35, and inhibits SC35-promoted tau exon 10 inclusion. Substituting K52 residue of SC35 by arginine impairs the role of SC35 in tau exon 10 inclusion. These results suggest that SIRT1 may serve as a therapeutic target for tauopathy by regulating SC35-mediated tau exon 10 splicing. PubMed:29226865

Appears in Networks:

p(HGNC:SIRT1) decreases p(HGNC:NFE2L2, pmod(Ac)) View Subject | View Object

Sirtuin 1 (SIRT1) was shown to decrease acetylation of Nrf2, as well as Nrf2-dependent transcription. PubMed:22020111

Appears in Networks:

p(HGNC:SIRT1) decreases p(HGNC:MAPT, pmod(Ac, Lys)) View Subject | View Object

Tau can be acetylated by the P300 acetyltransferase or by CREB-binding protein at several Lys residues in the flanking region or the repeat domain, and deacetylated at these sites by sirtuin 1 (SIRT1) and histone deacetylase 6 (HDAC6), respectively PubMed:26631930

Appears in Networks:

p(HGNC:SIRT1) decreases act(complex(GO:"NF-kappaB complex")) View Subject | View Object

Furthermore, negative regulators of NF-κB such as the NAD+- dependent histone deacetylase – SIRT1, abolish the deleterious neurotoxic effects of Amyloid-β PubMed:28745240

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

p(HGNC:SIRT1) decreases path(HBP:neurotoxicity) View Subject | View Object

Furthermore, negative regulators of NF-κB such as the NAD+- dependent histone deacetylase – SIRT1, abolish the deleterious neurotoxic effects of Amyloid-β PubMed:28745240

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

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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.