General Information:

Id: 5,266 (click here to show other Interactions for entry)
Diseases: Alzheimer disease - [OMIM]
Metabolic
Mus musculus
article/cited
Reference: Robin NC et al.(2013) Simvastatin Promotes Adult Hippocampal Neurogenesis by Enhancing Wnt/beta-Catenin Signaling Stem Cell Reports 2: 9-17 [PMID: 24511465]

Interaction Information:

Comment Oral administration of simvastatin in mice enhances Wnt signaling and that this elevation of Wnt signaling is required for the neurogenic effects of simvastatin.
Formal Description
Interaction-ID: 51321

drug/chemical compound

Simvastatin

increases_activity of

Drugbank entries Show/Hide entries for Simvastatin
Comment Statins enhance Wnt signaling through regulation of isoprenoid synthesis and not through cholesterol.
Formal Description
Interaction-ID: 51324

drug/chemical compound

Statin

increases_activity of

through regulation of isoprenoid synthesis and not through cholesterol
Comment Statins enhance Wnt signaling through regulation of isoprenoid synthesis and not through cholesterol.
Formal Description
Interaction-ID: 51327

affects_activity of

if regulated via statins
Comment Statins enhance Wnt signaling through regulation of isoprenoid synthesis and not through cholesterol-dependent mechanism.
Formal Description
Interaction-ID: 51332

drug/chemical compound

Cholesterol

NOT affects_activity of

via statins
Drugbank entries Show/Hide entries for Cholesterol
Comment Recently was reported that lovastatin and fluvastatin enhance Wnt signaling. (cited information)
Formal Description
Interaction-ID: 51338

drug/chemical compound

Lovastatin

increases_activity of

Drugbank entries Show/Hide entries for Lovastatin
Comment Recently was reported that lovastatin and fluvastatin enhance Wnt signaling. (cited information)
Formal Description
Interaction-ID: 51339

drug/chemical compound

Fluvastatin

increases_activity of

Drugbank entries Show/Hide entries for Fluvastatin
Comment Simva (=simvastatin) enhances Wnt signaling via depletion of isoprenoids and not cholesterol. Oral simva treatment enhances Wnt signaling in the mammalian adult hippocampus. This is significant in that aside from lithium, no other clinically approved compound has been demonstrated to enhance Wnt signaling in the brain. Addition of GGPP or FPP to simva-treated cells significantly reduced simva-mediated Wnt enhancement, while squalene did not have an effect. Since FPP is used to synthesize GGPP, the effect may be due to depletion of GGPP alone or a combination of FPP and GGPP depletion.
Formal Description
Interaction-ID: 51343

drug/chemical compound

Simvastatin

increases_activity of

in the mammalian adult hippocampus; via depletion of isoprenoids and not cholesterol
Drugbank entries Show/Hide entries for Simvastatin
Comment Providing initial insight, we show that HMGCR loss of function is sufficient to enhance the Wnt pathway. Furthermore, we demonstrate that simva acts on Wnt signaling by depleting isoprenoids, rather than through a cholesterol-dependent mechanism.
Formal Description
Interaction-ID: 51348

gene/protein

HMGCR

decreases_activity of

HMGCR loss of function is sufficient to enhance the Wnt pathway.
Drugbank entries Show/Hide entries for HMGCR
Comment Simva (=simvastatin) enhances Wnt signaling via depletion of isoprenoids and not cholesterol. Oral simva treatment enhances Wnt signaling in the mammalian adult hippocampus. This is significant in that aside from lithium, no other clinically approved compound has been demonstrated to enhance Wnt signaling in the brain. Addition of GGPP or FPP to simva-treated cells significantly reduced simva-mediated Wnt enhancement, while squalene did not have an effect. Since FPP is used to synthesize GGPP, the effect may be due to depletion of GGPP alone or a combination of FPP and GGPP depletion.
Formal Description
Interaction-ID: 51477

drug/chemical compound

Geranylgeranyl pyrophosphate

decreases_activity of

in the mammalian adult hippocampus; via depletion of isoprenoids and not cholesterol
Comment Simva (=simvastatin) enhances Wnt signaling via depletion of isoprenoids and not cholesterol. Oral simva treatment enhances Wnt signaling in the mammalian adult hippocampus. This is significant in that aside from lithium, no other clinically approved compound has been demonstrated to enhance Wnt signaling in the brain. Addition of GGPP or FPP to simva-treated cells significantly reduced simva-mediated Wnt enhancement, while squalene did not have an effect. Since FPP is used to synthesize GGPP, the effect may be due to depletion of GGPP alone or a combination of FPP and GGPP depletion.
Formal Description
Interaction-ID: 51478

drug/chemical compound

Farnesyl pyrophosphate

decreases_activity of