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p(HGNC:PSEN1)

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Entity

Name
PSEN1
Namespace
hgnc
Namespace Version
20180828
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/1b20f0637c395f8aa89c2e2e342d7b704062c242/external/hgnc-symbols.belns

Appears in Networks 11

Amyloid Precursor Protein Trafficking, Processing, and Function v1.0.0

Amyloid Precursor Protein Trafficking, Processing, and Function by Thinakaran, et al., 2008

APP processing in Alzheimer's disease v1.0.1

APP processing in Alzheimer's disease

Proteolytic processing of Alzeimer's beta-amyloid precursor protein v1.0.1

Nicotinic acetylcholine receptor signalling: roles in Alzheimer's disease and amyloid neuroprotection. v1.0.0

The Ubiquitin Proteasome System in Neurodegenerative Diseases: Sometimes the Chicken, Sometimes the Egg v1.0.0

Tau clearance mechanisms and their possible role in the pathogenesis of Alzheimer disease v1.0.0

Tau Protein Hyperphosphorylation and Aggregation in Alzheimer’s Disease and Other Tauopathies, and Possible Neuroprotective Strategies v1.0.0

Tau Modifications v1.9.5

Tau Modifications Sections of NESTOR

Alzheimer’s disease and the autophagic-lysosomal system v1.0.0

The Ubiquitin–Proteasome System and the Autophagic–Lysosomal System in Alzheimer Disease 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 10

complex(FPLX:"Gamma_secretase") hasComponent p(HGNC:PSEN1) View Subject | View Object

Appears in Networks:

a(CHEBI:testosterone) decreases p(HGNC:PSEN1) View Subject | View Object

However, a recent study blocking the conversion of testosterone to estrogen found an estrogen-independent improvement in cognitive function and lowering of plaque formation along with a decrease in BACE1 mRNA, protein level, and activity [211]. In addition, testosterone may also reduce the protein level of PS1 [196] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Cell Membrane
Confidence
Medium
MeSH
Hippocampus
MeSH
Down Syndrome

complex(p(HGNC:APP), p(HGNC:KIF5B)) regulates act(p(HGNC:PSEN1)) View Subject | View Object

During its transport, APP was found to interact with kinesin-I and functions as a kinesin-I membrane receptor to mediate axonal transport of beta-secretase (BACE1) and PS1 [26,27] PubMed:21214928

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

complex(p(HGNC:PLD1), p(HGNC:PSEN1)) hasComponent p(HGNC:PSEN1) View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") association p(HGNC:PSEN1) View Subject | View Object

APP and APP/presenilin-1 (PS-1) mice do not show neurodegeneration (Irizarry et al., 1997) and yet show several features of AD, including accumulation of plaques and defects in learning (Hsiao et al., 1996), suggesting that many features of AD are not the result of neuronal loss. These animals nonetheless have swollen cholinergic nerve terminals at 12 months, suggesting defective nerve sprouting (Hernandez et al., 2001). PubMed:19293145

Appears in Networks:

path(MESH:"Alzheimer disease, familial, type 3") association p(HGNC:PSEN1) View Subject | View Object

It is well established that mutations in PS1 result in familial AD, and until recently it was thought that this was only due to alterations in APP processing. PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

bp(GO:"calcium ion homeostasis") association p(HGNC:PSEN1) View Subject | View Object

Furthermore, presenilin-1, the most common mutation associated with early-onset familial AD (FAD), plays an essential role in calcium homeostasis and maintaining acidic lysosomal pH, with FAD-associated mutations disrupting calcium-dependent vATPase function in lysosomes [7,18–20] PubMed:29758300

Appears in Networks:

bp(GO:"regulation of lysosomal lumen pH") association p(HGNC:PSEN1) View Subject | View Object

Furthermore, presenilin-1, the most common mutation associated with early-onset familial AD (FAD), plays an essential role in calcium homeostasis and maintaining acidic lysosomal pH, with FAD-associated mutations disrupting calcium-dependent vATPase function in lysosomes [7,18–20] PubMed:29758300

Appears in Networks:

p(HGNC:UBQLN1) regulates deg(p(HGNC:PSEN1)) View Subject | View Object

Ubiquilin-1 interacts with both proteasomes and ubiquitinated proteins and regulates the proteasomal degradation of various proteins, including presenilin 1 (Haapasalo et al. 2010). PubMed:22908190

Appears in Networks:

complex(GO:"NF-kappaB complex") regulates p(HGNC:PSEN1) View Subject | View Object

In addition to augmenting γ-secretase activity, NF-κB also regulates the expression of the PS1 subunit of the γ-secretase complex PubMed:28745240

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

Out-Edges 14

p(HGNC:PSEN1) regulates p(HGNC:APP) View Subject | View Object

We and others have shown that PS1 can also regulate the intracellular trafficking of APP PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
High
MeSH
Hippocampus
MeSH
Down Syndrome

p(HGNC:PSEN1) hasVariant p(HGNC:PSEN1, var("?")) View Subject | View Object

Appears in Networks:

p(HGNC:PSEN1) causesNoChange path(HBP:Neurodegeneration) View Subject | View Object

APP and APP/presenilin-1 (PS-1) mice do not show neurodegeneration (Irizarry et al., 1997) and yet show several features of AD, including accumulation of plaques and defects in learning (Hsiao et al., 1996), suggesting that many features of AD are not the result of neuronal loss. These animals nonetheless have swollen cholinergic nerve terminals at 12 months, suggesting defective nerve sprouting (Hernandez et al., 2001). PubMed:19293145

Appears in Networks:

p(HGNC:PSEN1) association path(MESH:"Alzheimer Disease") View Subject | View Object

APP and APP/presenilin-1 (PS-1) mice do not show neurodegeneration (Irizarry et al., 1997) and yet show several features of AD, including accumulation of plaques and defects in learning (Hsiao et al., 1996), suggesting that many features of AD are not the result of neuronal loss. These animals nonetheless have swollen cholinergic nerve terminals at 12 months, suggesting defective nerve sprouting (Hernandez et al., 2001). PubMed:19293145

Appears in Networks:

p(HGNC:PSEN1) association path(MESH:"Alzheimer disease, familial, type 3") View Subject | View Object

It is well established that mutations in PS1 result in familial AD, and until recently it was thought that this was only due to alterations in APP processing. PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:PSEN1) increases bp(GO:"vacuolar acidification") View Subject | View Object

Mutations in PS1 were shown to impair the acidification of lysosomes, which is necessary for activating the proteolytic enzymes in this compartment. Improper acidification and impaired proteolysis of substrates would compromise the autophagy system and result in the accumulation of AVs as described above. PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:PSEN1) hasVariant p(HGNC:PSEN1, var("p.Gly183Val")) View Subject | View Object

Appears in Networks:

p(HGNC:PSEN1) hasVariant p(HGNC:PSEN1, var("p.Ala246Glu")) View Subject | View Object

Appears in Networks:

p(HGNC:PSEN1) hasVariant p(HGNC:PSEN1, var("p.Met146Leu")) View Subject | View Object

Appears in Networks:

p(HGNC:PSEN1) association bp(GO:"calcium ion homeostasis") View Subject | View Object

Furthermore, presenilin-1, the most common mutation associated with early-onset familial AD (FAD), plays an essential role in calcium homeostasis and maintaining acidic lysosomal pH, with FAD-associated mutations disrupting calcium-dependent vATPase function in lysosomes [7,18–20] PubMed:29758300

Appears in Networks:

p(HGNC:PSEN1) association bp(GO:"regulation of lysosomal lumen pH") View Subject | View Object

Furthermore, presenilin-1, the most common mutation associated with early-onset familial AD (FAD), plays an essential role in calcium homeostasis and maintaining acidic lysosomal pH, with FAD-associated mutations disrupting calcium-dependent vATPase function in lysosomes [7,18–20] PubMed:29758300

Appears in Networks:

p(HGNC:PSEN1) increases bp(GO:"pH reduction") View Subject | View Object

Beyond its role as a component of g-secretase, Presenilin 1 (PS1) is required for lysosome acidification, which is needed to activate cathepsins and other hydrolases that carry out digestion during autophagy (Lee et al. 2010). PubMed:22908190

Appears in Networks:
Annotations
MeSH
Lysosomes

p(HGNC:PSEN1) increases act(a(MESH:Cathepsins)) View Subject | View Object

Beyond its role as a component of g-secretase, Presenilin 1 (PS1) is required for lysosome acidification, which is needed to activate cathepsins and other hydrolases that carry out digestion during autophagy (Lee et al. 2010). PubMed:22908190

Appears in Networks:
Annotations
MeSH
Lysosomes

p(HGNC:PSEN1) increases p(HGNC:ATP6V0A1, pmod(NGlyco)) View Subject | View Object

In the absence of PS1, the V0a1 subunit of v-ATPase is not N-glycosylated in the ER and is degraded before sufficient amounts can be delivered to autolysosomes/lysosomes to support lysosomal acidification. PubMed:22908190

Appears in Networks:
Annotations
MeSH
Lysosomes

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

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.