General Information:

Id: 7,308
Diseases: Alzheimer disease - [OMIM]
Metabolic
Homo sapiens
article/cited
Reference: Couttas TA et al.(2014) Loss of the neuroprotective factor Sphingosine 1-phosphate early in Alzheimers disease pathogenesis Acta Neuropathol Commun 2: 9 [PMID: 24456642]

Interaction Information:

Comment Sphingosine 1-Phosphate Phosphatases 1 and 2 (SGPP1 and SGPP2) specifically catalyse the dephosphorylation of S1P.
Formal Description
Interaction-ID: 71690

gene/protein

SGPP1

decreases_phosphorylation of

drug/chemical compound

Sphingosine 1-phosphate

Comment Sphingosine 1-Phosphate Phosphatases 1 and 2 (SGPP1 and SGPP2) specifically catalyse the dephosphorylation of S1P.
Formal Description
Interaction-ID: 71691

gene/protein

SGPP2

decreases_phosphorylation of

drug/chemical compound

Sphingosine 1-phosphate

Comment S1P levels decline during AD pathogenesis in human hippocampus (A), inferior temporal GM (B), inferior temporal WM (C), superior frontal GM (D), superior frontal WM (E), and cerebellum.
Formal Description
Interaction-ID: 71692

disease

Alzheimer disease

decreases_quantity of

drug/chemical compound

Sphingosine 1-phosphate

in human AD hippocampus, inferior temporal GM, inferior temporal WM, superior frontal GM, superior frontal WM, and cerebellum.
Comment ApoE regulates secretion of the potent neuroprotective signaling lipid Sphingosine 1-phosphate (S1P). S1P is derived by phosphorylation of sphingosine, catalysed by sphingosine kinases 1 and 2 (SphK1 and 2), and SphK1 positively regulates glutamate secretion and synaptic strength in hippocampal neurons(cited information). Hippocampal S1P level is related to APOE genotype.
Formal Description
Interaction-ID: 71693

gene/protein

APOE

affects_quantity of

drug/chemical compound

Sphingosine 1-phosphate

in hippocampus; via secretion; the quantity is depending on the APOE isoform.
Drugbank entries Show/Hide entries for APOE
Comment ApoE regulates secretion of the potent neuroprotective signaling lipid Sphingosine 1-phosphate (S1P). S1P is derived by phosphorylation of sphingosine, catalysed by sphingosine kinases 1 and 2 (SphK1 and 2), and SphK1 positively regulates glutamate secretion and synaptic strength in hippocampal neurons. (cited information)
Formal Description
Interaction-ID: 71694

drug/chemical compound

Sphingosine 1-phosphate

increases_activity of

process

negative regulation of neuron death

Comment S1P is derived by phosphorylation of sphingosine, catalysed by sphingosine kinases 1 and 2 (SphK1 and 2), and SphK1 positively regulates glutamate secretion and synaptic strength in hippocampal neurons. (cited information)
Formal Description
Interaction-ID: 71695

gene/protein

SPHK1

increases_quantity of

drug/chemical compound

Sphingosine 1-phosphate

via phosphorylation of sphingosine.
Comment ApoE regulates secretion of the potent neuroprotective signaling lipid Sphingosine 1-phosphate (S1P). S1P is derived by phosphorylation of sphingosine, catalysed by sphingosine kinases 1 and 2 (SphK1 and 2), and SphK1 positively regulates glutamate secretion and synaptic strength in hippocampal neurons. (cited information)
Formal Description
Interaction-ID: 71696

gene/protein

SPHK2

increases_quantity of

drug/chemical compound

Sphingosine 1-phosphate

via phosphorylation of sphingosine.
Comment SphK1 positively regulates glutamate secretion and synaptic strength in hippocampal neurons. (cited information)
Formal Description
Interaction-ID: 71697

gene/protein

SPHK1

increases_quantity of

drug/chemical compound

Glutamate

in hippocampal neurons; via secretion
Comment SphK1 positively regulates glutamate secretion and synaptic strength in hippocampal neurons. (cited information)
Formal Description
Interaction-ID: 71698

gene/protein

SPHK1

affects_activity of

cellular component

synapse

in hippocampal neurons
Comment S1P is essential for development of the neural tube and vascular system during embryogenesis. It is a potent cytoprotective factor that has been shown to protect cultured cortical neurons against Abeta toxicity. Signalling through pre-synaptic S1P3 receptors, S1P also stimulates glutamate secretion in hippocampal neurons, promoting long-term potentiation and memory consolidation. Similarly SphK1 localised to pre-synaptic terminals is required for neurotransmitter release and charge transfer in response to acetylcholine stimulation. (cited information)
Formal Description
Interaction-ID: 71699

drug/chemical compound

Sphingosine 1-phosphate

increases_activity of

process

neural tube development

during embryogenesis
Comment S1P is essential for development of the neural tube and vascular system during embryogenesis. It is a potent cytoprotective factor that has been shown to protect cultured cortical neurons against Abeta toxicity. Signalling through pre-synaptic S1P3 receptors, S1P also stimulates glutamate secretion in hippocampal neurons, promoting long-term potentiation and memory consolidation. Similarly SphK1 localised to pre-synaptic terminals is required for neurotransmitter release and charge transfer in response to acetylcholine stimulation. (cited information)
Formal Description
Interaction-ID: 71700

drug/chemical compound

Sphingosine 1-phosphate

increases_activity of

process

vasculature development

during embryogenesis
Comment S1P is essential for development of the neural tube and vascular system during GO:0001944. It is a potent cytoprotective factor that has been shown to protect cultured cortical neurons against Abeta toxicity. Signalling through pre-synaptic S1P3 receptors, S1P also stimulates glutamate secretion in hippocampal neurons, promoting long-term potentiation and memory consolidation. Similarly SphK1 localised to pre-synaptic terminals is required for neurotransmitter release and charge transfer in response to acetylcholine stimulation. (cited information)
Formal Description
Interaction-ID: 71701

drug/chemical compound

Sphingosine 1-phosphate

increases_activity of

process

embryo development

Comment S1P is essential for development of the neural tube and vascular system during embryogenesis. It is a potent cytoprotective factor that has been shown to protect cultured cortical neurons against Abeta toxicity. Signalling through pre-synaptic S1P3 receptors, S1P also stimulates glutamate secretion in hippocampal neurons, promoting long-term potentiation and memory consolidation. Similarly SphK1 localised to pre-synaptic terminals is required for neurotransmitter release and charge transfer in response to acetylcholine stimulation. (cited information)
Formal Description
Interaction-ID: 71702

drug/chemical compound

Sphingosine 1-phosphate

decreases_activity of

gene/protein

Amyloid beta peptide

against Abeta toxicity
Comment S1P is essential for development of the neural tube and vascular system during embryogenesis. It is a potent cytoprotective factor that has been shown to protect cultured cortical neurons against Abeta toxicity. Signalling through pre-synaptic S1P3 receptors, S1P also stimulates glutamate secretion in hippocampal neurons, promoting long-term potentiation and memory consolidation. Similarly SphK1 localised to pre-synaptic terminals is required for neurotransmitter release and charge transfer in response to acetylcholine stimulation. (cited information)
Formal Description
Interaction-ID: 71703

drug/chemical compound

Sphingosine 1-phosphate

increases_quantity of

drug/chemical compound

Glutamate

in hippocampal neurons; via signalling through pre-synaptic S1P3 receptors and secretion.
Comment S1P is essential for development of the neural tube and vascular system during embryogenesis. It is a potent cytoprotective factor that has been shown to protect cultured cortical neurons against Abeta toxicity. Signalling through pre-synaptic S1P3 receptors, S1P also stimulates glutamate secretion in hippocampal neurons, promoting long-term potentiation and memory consolidation. Similarly SphK1 localised to pre-synaptic terminals is required for neurotransmitter release and charge transfer in response to acetylcholine stimulation. (cited information)
Formal Description
Interaction-ID: 71704

drug/chemical compound

Sphingosine 1-phosphate

increases_activity of

process

long-term synaptic potentiation

Comment S1P is essential for development of the neural tube and vascular system during embryogenesis. It is a potent cytoprotective factor that has been shown to protect cultured cortical neurons against Abeta toxicity. Signalling through pre-synaptic S1P3 receptors, S1P also stimulates glutamate secretion in hippocampal neurons, promoting long-term potentiation and memory consolidation. Similarly SphK1 localised to pre-synaptic terminals is required for neurotransmitter release and charge transfer in response to acetylcholine stimulation. (cited information)
Formal Description
Interaction-ID: 71705

drug/chemical compound

Sphingosine 1-phosphate

increases_activity of

process

memory

via memory consolidation
Comment S1P is essential for development of the neural tube and vascular system during embryogenesis. It is a potent cytoprotective factor that has been shown to protect cultured cortical neurons against Abeta toxicity. Signalling through pre-synaptic S1P3 receptors, S1P also stimulates glutamate secretion in hippocampal neurons, promoting long-term potentiation and memory consolidation. Similarly SphK1 localised to pre-synaptic terminals is required for neurotransmitter release and charge transfer in response to acetylcholine stimulation. (cited information)
Formal Description
Interaction-ID: 71706

gene/protein

SPHK1

increases_activity of

process

neurotransmitter secretion

Comment Loss of S1P proceeds in tandem with the development of NFT (neurofibrillary tangles) pathology, coupled to a decline in the activity of sphingosine kinases, which catalyse S1P synthesis.
Formal Description
Interaction-ID: 71707

drug/chemical compound

Sphingosine 1-phosphate

decreases_quantity of

phenotype

neurofibrillary tangles

Comment Over 99% of AD cases are the age-related, late onset form of the disease, for which the greatest genetic risk factor is the APOE4 allele. Apolipoprotein E (ApoE) is a major lipid transport protein of the central nervous system (CNS) that also mediates the transport and clearance of Abeta. Homozygous carriers of the APOE4 allele have a 12-fold increased risk of developing AD, compared with non-carriers. (cited information)
Formal Description
Interaction-ID: 71708

gene/protein mutant

APOE (isoform E4)

increases_activity of

disease

Alzheimer disease

Comment Ceramide levels are not significantly altered in hippocampus and temporal GM during AD pathogenesis.
Formal Description
Interaction-ID: 71710

disease

Alzheimer disease

NOT affects_quantity of

drug/chemical compound

N-Acylsphingosine

in AD hippocampus and temporal GM (Grey Matter) tissue
Comment This study demonstrates loss of S1P and sphingosine kinase activity early in AD pathogenesis, and prior to AD diagnosis.
Formal Description
Interaction-ID: 71711

disease

Alzheimer disease

decreases_activity of

gene/protein

SPHK1

early in AD pathogenesis
Comment SphK2 activity declines during AD pathogenesis.
Formal Description
Interaction-ID: 71712

disease

Alzheimer disease

decreases_activity of

gene/protein

SPHK2

in AD hippocampus and temporal GM (Grey Matter) tissue
Comment S1P phosphatase (SGPP1) activity increases in temporal grey matter of AD brains.
Formal Description
Interaction-ID: 71713

disease

Alzheimer disease

increases_activity of

gene/protein

SGPP1

in temporal GM (Grey Matter)
Comment S1P phosphatase (SGPP1) activity increases in temporal GM of AD brains. Despite declining SphK2 activity with increasing NFT pathology, none of SphK1, SphK2, or S1P phosphatase activity were significantly correlated with S1P/sphingosine in temporal GM (Grey Matter).
Formal Description
Interaction-ID: 71714

disease

Alzheimer disease

increases_activity of

gene/protein

SGPP2

in temporal GM (Grey Matter)
Comment S1P/sphingosine ratio was 2.5-fold higher in hippocampus of ApoE2 carriers compared to ApoE4 carriers, and multivariate regression showed a significant association between APOE genotype and hippocampal S1P/sphingosine (p‚ÄČ=‚ÄČ0.0495), suggesting a new link between APOE genotype and pre-disposition to AD.
Formal Description
Interaction-ID: 71715

gene/protein mutant

APOE (isoform E2)

increases_activity of

phenotype

S1P/sphingosine ratio

in hippocampus
Comment S1P/sphingosine ratio was 2.5-fold higher in hippocampus of ApoE2 carriers compared to ApoE4 carriers, and multivariate regression showed a significant association between APOE genotype and hippocampal S1P/sphingosine (p‚ÄČ=‚ÄČ0.0495), suggesting a new link between APOE genotype and pre-disposition to AD.
Formal Description
Interaction-ID: 71716

gene/protein mutant

APOE (isoform E4)

decreases_activity of

phenotype

S1P/sphingosine ratio

in hippocampus
Comment Sphingosine 1-phosphate (S1P) is a potent lipid signalling molecule that associates with ApoE in high density lipoprotein (HDL) complexes in the CNS. (cited information)
Formal Description
Interaction-ID: 71717

drug/chemical compound

Sphingosine 1-phosphate

interacts (colocalizes) with

gene/protein

APOE

in the CNS; in high density lipoprotein (HDL) complexes
Drugbank entries Show/Hide entries for APOE
Comment Sphingosine 1-phosphate (S1P) is a potent lipid signalling molecule that associates with ApoE in high density lipoprotein (HDL) complexes in the CNS. (cited information)
Formal Description
Interaction-ID: 71718

drug/chemical compound

Sphingosine 1-phosphate

interacts (colocalizes) with

complex/PPI

HDL

in the CNS; associated with ApoE
Comment S1P is derived by phosphorylation of sphingosine, catalysed by sphingosine kinases 1 and 2 (SphK1 and 2), and SphK1 positively regulates glutamate secretion and synaptic strength in hippocampal neurons. (cited information)
Formal Description
Interaction-ID: 80534

gene/protein

SPHK1

increases_phosphorylation of

drug/chemical compound

Sphingosine

Drugbank entries Show/Hide entries for
Comment S1P is derived by phosphorylation of sphingosine, catalysed by sphingosine kinases 1 and 2 (SphK1 and 2), and SphK1 positively regulates glutamate secretion and synaptic strength in hippocampal neurons. (cited information)
Formal Description
Interaction-ID: 80535

gene/protein

SPHK2

increases_phosphorylation of

drug/chemical compound

Sphingosine

Drugbank entries Show/Hide entries for