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p(HGNC:CHRNA4)

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Entity

Name
CHRNA4
Namespace
hgnc
Namespace Version
20180906
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

Appears in Networks 13

albuquerque2009 v1.0.0

This file encodes the article Mammalian Nicotinic Acetylcholine Receptors: From Structure to Function by Albuquerque et al, 2009

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

The Nicotinic Acetylcholine Receptor: The Founding Father of the Pentameric Ligand-gated Ion Channel Superfamily v1.0.1

Nicotinic Acetylcholine Receptors and Nicotinic Cholinergic Mechanisms of the Central Nervous System v1.0.0

Alzheimer's Disease: Targeting the Cholinergic System v1.0.0

Role of the nicotinic acetylcholine receptor in Alzheimer's disease pathology and treatment v1.0.1

NACHO Mediates Nicotinic Acetylcholine Receptor Function throughout the Brain v1.0.0

Neural Systems Governed by Nicotinic Acetylcholine Receptors: Emerging Hypotheses v1.0.0

Cholinergic system during the progression of Alzheimer’s disease: therapeutic implications v1.0.0

Nicotinic Receptor Abnormalities of Alzheimer’s Disease: Therapeutic Implications v1.0.0

Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system v1.0.0

This document contains the curation of the review article Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system by Taly et al. 2009

Chaperoning α7 neuronal nicotinic acetylcholine receptors v1.0.0

Neuronal and Extraneuronal Nicotinic Acetylcholine Receptors. v1.0.0

In-Edges 28

a(CHEBI:"NS-398") decreases p(HGNC:CHRNA4) View Subject | View Object

A link between alpha4 nAChRs and Cox2 was suggested by the observation that interneurons in the hippocampus coexpress both proteins (165). A mechanistic connection was inferred when long-term treatment of aged animals with NS398 promoted retention of alpha4 nAChR expression in the brain, an effect that was antagonized by the coadministration of nicotine. PubMed:19126755

Appears in Networks:
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Text Location
Review

complex(p(HGNC:CHRNA4), p(HGNC:CHRNB2)) hasComponent p(HGNC:CHRNA4) View Subject | View Object

Appears in Networks:

composite(p(HGNC:CHRNA4), p(HGNC:CHRNA6), p(HGNC:CHRNB2), p(HGNC:CHRNB3)) hasComponent p(HGNC:CHRNA4) View Subject | View Object

Appears in Networks:

composite(p(HGNC:CHRNA4), p(HGNC:CHRNA7), p(HGNC:CHRNB2)) hasComponent p(HGNC:CHRNA4) View Subject | View Object

Appears in Networks:

p(HGNC:PTGS2) association p(HGNC:CHRNA4) View Subject | View Object

A link between alpha4 nAChRs and Cox2 was suggested by the observation that interneurons in the hippocampus coexpress both proteins (165). A mechanistic connection was inferred when long-term treatment of aged animals with NS398 promoted retention of alpha4 nAChR expression in the brain, an effect that was antagonized by the coadministration of nicotine. PubMed:19126755

Appears in Networks:
Annotations
Text Location
Review

path(MESH:"Alzheimer Disease") negativeCorrelation p(HGNC:CHRNA4) View Subject | View Object

However, loss of brain nAChRs precedes that of muscarinic receptors during normal aging, and it is often much more extensive in human brains afflicted with AD relative to age-matched controls (236, 308, 373, 374, 416, 519). In fact, alpha4 nAChR expression can decrease by >80% in the AD brain (306, 374). PubMed:19126755

Appears in Networks:
Annotations
Text Location
Review

a(CHEBI:"amyloid-beta") positiveCorrelation p(HGNC:CHRNA4) View Subject | View Object

In addition, not only have alpha7 nAChRs been found colocalized with plaques (Wang et al., 2000b) but alpha7 and alpha4 subunits are also positively correlated with neurons that accumulate Abeta (Wevers et al., 1999). PubMed:19293145

Appears in Networks:
Annotations
MeSH
Neurons

a(CHEBI:"amyloid-beta") increases p(HGNC:CHRNA4) View Subject | View Object

Similar effects of Abeta on nAChR expression have been confirmed in studies using cultured cells; Abeta causes a reduced expression of nAChRs in PC12 cells (Guan et al., 2001), and alpha4, alpha3, and alpha7 expression are all increased in cultured rat astrocytes (Xiu et al., 2005). PubMed:19293145

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Annotations
MeSH
Astrocytes

a(CHEBI:donepezil) increases p(HGNC:CHRNA4) View Subject | View Object

Donepezil, which protects cultured rat cortical neurons, when applied for 4 days resulted in an up-regulation of alpha4 and alpha7 nAChRs with the result that donepezil was even more potently protective (Kume et al., 2005). PubMed:19293145

Appears in Networks:

bp(GO:"lipid metabolic process") association p(HGNC:CHRNA4) View Subject | View Object

The loss of alpha4 subunits was suggested to be related to lipid peroxidation, because the loss correlated with the level of peroxidation in the temporal cortex of brains from patients with AD, suggesting that receptor loss may be caused by oxidation of proteins (Yu et al., 2003). PubMed:19293145

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

complex(p(HGNC:CHRNA4), p(HGNC:CHRNA5), p(HGNC:CHRNB2)) hasComponent p(HGNC:CHRNA4) View Subject | View Object

Appears in Networks:

complex(a(MESH:Bungarotoxins), p(HGNC:CHRNA4)) hasComponent p(HGNC:CHRNA4) View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") decreases p(HGNC:CHRNA4) View Subject | View Object

Similar results have been obtained using subtype-specific antibodies. Binding of monoclonal antibodies raised against the alpha4 or the alpha7 subunit, for example, was significantly reduced in post mortem cortices of five patients with AD compared with five patients without AD of similar age (Burghaus et al., 2000). In one study, Western blots confirmed that the greatest reduction was in alpha4 (Guan et al., 2000). Likewise, subunit-specific antibodies reveal a reduced expression of alpha4 but not alpha3 or alpha7 in brains from patients with AD (Martin-Ruiz et al., 1999) PubMed:19293145

Appears in Networks:

path(MESH:"Alzheimer Disease") decreases p(HGNC:CHRNA4) View Subject | View Object

Thus, predominantly alpha4 and alpha7 subunits, and to a lesser extent alpha3 subunits, are lost in AD, although there are tissue-specific differences to this pattern, such as the upregulation of nAChRs on astrocytes. PubMed:19293145

Appears in Networks:

path(MESH:"Alzheimer Disease") decreases p(HGNC:CHRNA4) View Subject | View Object

Thus, in brains from patients with AD and in neurons responding to exogenously applied Abeta, there is a reduction in expression of nAChR subunits, especially alpha4, alpha7, beta4, and possibly alpha3. Although AD may also involve changes in expression of other ligand-gated ion channels— for example, the expression of NMDA receptors (Bi and Sze, 2002; Jacob et al., 2007), alpha-amino-3-hydroxy- 5-methyl-4-isoxazolepropionic acid receptors (Jacob et al., 2007), and beta3 GABA receptor subunits are all reduced (Mizukami et al., 1998)—there is abundant evidence of a loss of nAChR subunits in AD possibly caused by the actions of Abeta. PubMed:19293145

Appears in Networks:
Annotations
MeSH
Brain

bp(GO:"intracellular receptor signaling pathway") association p(HGNC:CHRNA4) View Subject | View Object

The cytoplasmic domain of the alpha􏰀4-nAChR subunit also binds a variety of scaffold proteins that interact with cytoskeletal proteins and with G protein systems that are involved in intracellular signaling pathways PubMed:23038257

Appears in Networks:

p(MESH:"Cytoskeletal Proteins") association p(HGNC:CHRNA4) View Subject | View Object

The cytoplasmic domain of the alpha􏰀4-nAChR subunit also binds a variety of scaffold proteins that interact with cytoskeletal proteins and with G protein systems that are involved in intracellular signaling pathways PubMed:23038257

Appears in Networks:

a(CHEBI:"amyloid-beta") positiveCorrelation p(HGNC:CHRNA4) View Subject | View Object

This prospect was supported by the finding that α7 nAChRs were found in plaques (159), and α7 and α4 subunits positively correlated with neurons that accumulated Aβ and hyperphosphorylated tau in AD brain tissue (161). PubMed:17009926

Appears in Networks:
Annotations
Cell Ontology (CL)
neuron
MeSH
Brain
MeSH
Alzheimer Disease

p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) positiveCorrelation p(HGNC:CHRNA4) View Subject | View Object

This prospect was supported by the finding that α7 nAChRs were found in plaques (159), and α7 and α4 subunits positively correlated with neurons that accumulated Aβ and hyperphosphorylated tau in AD brain tissue (161). PubMed:17009926

Appears in Networks:
Annotations
Cell Ontology (CL)
neuron
MeSH
Brain
MeSH
Alzheimer Disease

p(FPLX:CHRN) hasMember p(HGNC:CHRNA4) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRNA4), p(HGNC:CHRNA4), p(HGNC:CHRNB2), p(HGNC:CHRNB2), p(HGNC:CHRNB2)) hasComponent p(HGNC:CHRNA4) View Subject | View Object

Appears in Networks:

p(GFAM:"Cholinergic receptors nicotinic subunits") hasMember p(HGNC:CHRNA4) View Subject | View Object

Appears in Networks:

complex(a(CHEBI:cytisine), p(HGNC:CHRNA4)) hasComponent p(HGNC:CHRNA4) View Subject | View Object

Appears in Networks:

complex(a(CHEBI:epibatidine), p(HGNC:CHRNA4)) hasComponent p(HGNC:CHRNA4) View Subject | View Object

Appears in Networks:

complex(a(CHEBI:nicotine), p(HGNC:CHRNA4)) hasComponent p(HGNC:CHRNA4) View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") negativeCorrelation p(HGNC:CHRNA4) View Subject | View Object

A decrease in the protein levels of the alpha3 and alpha4 nAChR subunits was recently measured in the temporal cortex and of the alpha3, alpha4, and alpha7 nAChR subtypes in the hippocampi of AD brains relative to age-matched control subjects (Guan et al 2000b) PubMed:11230871

Appears in Networks:
Annotations
MeSH
Temporal Lobe

complex(p(HGNC:CHRNA4), p(HGNC:CHRNA6), p(HGNC:CHRNB2), p(HGNC:CHRNB3)) hasComponent p(HGNC:CHRNA4) View Subject | View Object

Appears in Networks:

complex(p(HGNC:CHRNA4), p(HGNC:RIC3)) hasComponent p(HGNC:CHRNA4) View Subject | View Object

Appears in Networks:

Out-Edges 17

p(HGNC:CHRNA4) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

However, loss of brain nAChRs precedes that of muscarinic receptors during normal aging, and it is often much more extensive in human brains afflicted with AD relative to age-matched controls (236, 308, 373, 374, 416, 519). In fact, alpha4 nAChR expression can decrease by >80% in the AD brain (306, 374). PubMed:19126755

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:CHRNA4) association p(HGNC:PTGS2) View Subject | View Object

A link between alpha4 nAChRs and Cox2 was suggested by the observation that interneurons in the hippocampus coexpress both proteins (165). A mechanistic connection was inferred when long-term treatment of aged animals with NS398 promoted retention of alpha4 nAChR expression in the brain, an effect that was antagonized by the coadministration of nicotine. PubMed:19126755

Appears in Networks:
Annotations
Text Location
Review

p(HGNC:CHRNA4) association bp(GO:"intracellular receptor signaling pathway") View Subject | View Object

The cytoplasmic domain of the alpha􏰀4-nAChR subunit also binds a variety of scaffold proteins that interact with cytoskeletal proteins and with G protein systems that are involved in intracellular signaling pathways PubMed:23038257

Appears in Networks:

p(HGNC:CHRNA4) positiveCorrelation a(CHEBI:"amyloid-beta") View Subject | View Object

In addition, not only have alpha7 nAChRs been found colocalized with plaques (Wang et al., 2000b) but alpha7 and alpha4 subunits are also positively correlated with neurons that accumulate Abeta (Wevers et al., 1999). PubMed:19293145

Appears in Networks:
Annotations
MeSH
Neurons

act(p(HGNC:CHRNA4)) decreases act(a(CHEBI:"L-glutamate(2-)")) View Subject | View Object

For example, alpha4-specific agonists protect porcine small retinal ganglion cells against L-glutamate toxicity (Thompson et al., 2006), whereas alpha7 nAChRs protect large retinal ganglion cells (Wehrwein et al., 2004) against L-glutamate toxicity. PubMed:19293145

Appears in Networks:
Annotations
MeSH
Retinal Ganglion Cells

act(p(HGNC:CHRNA4)) increases act(a(CHEBI:nicotine)) View Subject | View Object

For example, nicotine effectively protects wild-type mice, but not alpha4-knockout mice, against methamphetamine-evoked neurodegeneration (Ryan et al., 2001). PubMed:19293145

Appears in Networks:

p(HGNC:CHRNA4) association bp(GO:"lipid metabolic process") View Subject | View Object

The loss of alpha4 subunits was suggested to be related to lipid peroxidation, because the loss correlated with the level of peroxidation in the temporal cortex of brains from patients with AD, suggesting that receptor loss may be caused by oxidation of proteins (Yu et al., 2003). PubMed:19293145

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

p(HGNC:CHRNA4) association p(MESH:"Cytoskeletal Proteins") View Subject | View Object

The cytoplasmic domain of the alpha􏰀4-nAChR subunit also binds a variety of scaffold proteins that interact with cytoskeletal proteins and with G protein systems that are involved in intracellular signaling pathways PubMed:23038257

Appears in Networks:

p(HGNC:CHRNA4) hasVariant p(HGNC:CHRNA4, var("p.Ser248Thr")) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA4) positiveCorrelation a(CHEBI:"amyloid-beta") View Subject | View Object

This prospect was supported by the finding that α7 nAChRs were found in plaques (159), and α7 and α4 subunits positively correlated with neurons that accumulated Aβ and hyperphosphorylated tau in AD brain tissue (161). PubMed:17009926

Appears in Networks:
Annotations
Cell Ontology (CL)
neuron
MeSH
Brain
MeSH
Alzheimer Disease

p(HGNC:CHRNA4) positiveCorrelation p(HGNC:MAPT, pmod(HBP:hyperphosphorylation)) View Subject | View Object

This prospect was supported by the finding that α7 nAChRs were found in plaques (159), and α7 and α4 subunits positively correlated with neurons that accumulated Aβ and hyperphosphorylated tau in AD brain tissue (161). PubMed:17009926

Appears in Networks:
Annotations
Cell Ontology (CL)
neuron
MeSH
Brain
MeSH
Alzheimer Disease

p(HGNC:CHRNA4) increases a(MESH:"Receptors, Nicotinic") View Subject | View Object

On the other hand, neuronal nicotinic receptors are formed by the combination of only two types of subunits (α2-10 and β2-4) PubMed:26813123

Appears in Networks:
Annotations
MeSH
Neurons

p(HGNC:CHRNA4) hasVariant p(HGNC:CHRNA4, var("?")) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA4) decreases complex(a(CHEBI:cytisine), p(FPLX:CHRN)) View Subject | View Object

When the laminar binding distribution of [3H]nicotine, [3H]epibatidine, and [3H]cytisine was measured in AD cortical autopsy tissue, marked reductions were observed relative to control brains (Sihver et al 1999c) (Figure 1) PubMed:11230871

Appears in Networks:
Annotations
MeSH
Cerebral Cortex
MeSH
Alzheimer Disease

p(HGNC:CHRNA4) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

A decrease in the protein levels of the alpha3 and alpha4 nAChR subunits was recently measured in the temporal cortex and of the alpha3, alpha4, and alpha7 nAChR subtypes in the hippocampi of AD brains relative to age-matched control subjects (Guan et al 2000b) PubMed:11230871

Appears in Networks:
Annotations
MeSH
Temporal Lobe

p(HGNC:CHRNA4) hasVariant p(HGNC:CHRNA4, frag("331_600")) View Subject | View Object

Appears in Networks:

p(HGNC:CHRNA4) increases act(a(CHEBI:nicotine)) View Subject | View Object

in α4- and β2-knockout mice, the responses of raphe neurons to nicotine is abolished, together with nicotine-elicited antinociception228, and α4-hypersensitive knock-in mice show nicotine hypersensitivity in the supraspinal control (hot-plate assay), but not in the spinal control (tail flick assay)229. PubMed:19721446

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Annotations
Text Location
Review

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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.