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bp(GO:"neuron death")

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Entity

Name
neuron death
Namespace
go
Namespace Version
20180921
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/go-names.belns

Appears in Networks 32

Amyloid β oligomers (AβOs) in Alzheimer’s disease v1.0.0

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

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

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

M1 muscarinic acetylcholine receptor in Alzheimer’s disease v1.0.0

This file encodes the article M1 muscarinic acetylcholine receptor in Alzheimer’s disease by Jiang et al, 2014

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

Nuclear receptors as therapeutic targets for Alzheimer's disease. v1.0.0

Chaperoning α7 neuronal nicotinic acetylcholine receptors v1.0.0

Naturally-expressed nicotinic acetylcholine receptor subtypes v1.0.0

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

Structural and functional properties of prefibrillar α-synuclein oligomers v1.0.0

MMP-9 and MMP-2 Contribute to Neuronal Cell Death in iPSC Models of Frontotemporal Dementia with MAPT Mutations v1.0.0

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

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

Molecular chaperones and regulation of tau quality control: strategies for drug discovery in tauopathies v1.0.0

Tau protein aggregation is associated with cellular senescence in the brain v1.0.0

Tau oligomers-Cytotoxicity, propagation, and mitochondrial damage v1.0.0

Tau oligomers-Cytotoxicity, propagation, and mitochondrial damage from Shafiei et al., 2017

Tau Modifications v1.9.5

Tau Modifications Sections of NESTOR

Inflammasome Involvement in Alzheimer’s Disease v1.0.0

Amyloid-Binding Alcohol Dehydrogenase (ABAD) Inhibitors for the Treatment of Alzheimer’s Disease v1.0.0

Protein phosphatase 2A dysfunction in Alzheimer’s disease v1.0.0

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

Caenorhabditis elegans models of tauopathy v1.0.0

Tau in physiology and pathology v1.0.0

New insights into the role of microRNAs and long noncoding RNAs in most common neurodegenerative diseases 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

Phytochemicals as inhibitors of NF-κB for treatment of Alzheimer’s disease v1.0.0

Significance of NF-κB as a pivotal therapeutic target in the neurodegenerative pathologies of Alzheimer's disease and multiple sclerosis v1.0.0

mTOR-Related Brain Dysfunctions in Neuropsychiatric Disorders v1.0.0

In-Edges 77

a(HBP:HBP00018) causesNoChange bp(GO:"neuron death") View Subject | View Object

On the contrary, no relationship between total Aβ plaque burden and number of astrocytes or neurons was found (da Rocha-Souto et al. 2011). PubMed:29196815

Appears in Networks:
Annotations
MeSH
Extracellular Space
Cell Ontology (CL)
neuron
Confidence
High

a(HBP:HBP00074) increases bp(GO:"neuron death") View Subject | View Object

Moreover, it was postulated that AβOs may trigger a harmful cascade damaging neurons and synapses (Morris et al. 2014). PubMed:29196815

Appears in Networks:
Annotations
Confidence
High

a(HBP:HBP00074) increases bp(GO:"neuron death") View Subject | View Object

Soluble Aβ oligomers may cause a highly selective neuronal death accelerated by increasing exposure to AβOs (Lambert et al. 1998). PubMed:29196815

Appears in Networks:
Annotations
MeSH
Extracellular Space
Cell Ontology (CL)
neuron
Confidence
High

a(HBP:HBP00074) positiveCorrelation bp(GO:"neuron death") View Subject | View Object

In addition, the load of AβO deposits significantly correlated with fibrillar Aβ plaque deposition as well as with neuronal loss and numbers of astrocytes, although not with memory deficits. PubMed:29196815

Appears in Networks:
Annotations
MeSH
Extracellular Space
Cell Ontology (CL)
neuron
Confidence
High

a(CHEBI:"amyloid-beta") increases bp(GO:"neuron death") View Subject | View Object

Multiple lines of evidence demonstrate that overproduction of Abeta results in a neurodegenerative cascade leading to synaptic dysfunction, formation of intraneuronal fibrillary tangles and eventually neuron loss in affected areas of the brain [6,142] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
High
MeSH
Neurons

complex(a(HBP:HBP00042), p(HGNC:TNFRSF21)) association bp(GO:"neuron death") View Subject | View Object

Although sAPPbeta only differs from sAPPalpha by lacking the Abeta1-16 region at its carboxyl-terminus, sAPPbeta was reported to function as a death receptor 6 ligand and mediate axonal pruning and neuronal cell death [94] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
High
MeSH
Neurons

p(HGNC:BACE1) increases bp(GO:"neuron death") View Subject | View Object

BACE1 deficiency in AD model mice have been shown to rescue cholinergic dysfunction, neuronal loss and memory deficits, correlating with a dramatic reduction in Abeta40/42 levels [79-81] PubMed:21214928

Appears in Networks:
Annotations
MeSH
Endosomes
Confidence
Medium
MeSH
Neurons

a(CHEBI:"amyloid-beta") increases bp(GO:"neuron death") View Subject | View Object

Abeta toxicity can lead to synaptic dysfunction, neuronal cell death, impaired learning/memory and abnormal behaviors in AD models in vitro and in vivo PubMed:22122372

Appears in Networks:
Annotations
Confidence
High

a(CHEBI:"amyloid-beta") increases bp(GO:"neuron death") View Subject | View Object

Studies have demonstrated that Abeta overproduction leads to neurotoxicity, neuronal tangle formation, synaptic damage and eventually neuron loss in the pathologically affected brain regions (Selkoe 1998; Shankar and Walsh 2009) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

complex(p(HBP:HBP00042, frag("?")), p(HGNC:TNFRSF21)) increases bp(GO:"neuron death") View Subject | View Object

A recent study suggested that sAPP-beta can be cleaved to generate an N-terminal fragment that is a ligand for death receptor 6, activating caspase 6 which further stimulates axonal pruning and neuronal cell death (Nikolaev et al. 2009) PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Neurons

path(MESH:"Alzheimer Disease") association bp(GO:"neuron death") View Subject | View Object

Plaques consisting of beta-amyloid (Abeta) peptide (Selkoe 1998), neurofibrillary tangles consisting largely of hyperphosphorylated microtubule-associated tau protein (Buee et al. 2000; Gendron and Petrucelli 2009) and neuron loss in the hippocampus and cortex regions are the major pathological hallmarks of Alzheimer’s disease. PubMed:22122372

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex
MeSH
Hippocampus

a(CHEBI:nicotine) decreases bp(GO:"neuron death") View Subject | View Object

More direct evidence of the protective effects of nicotine in this disease process comes from studies in primates, where oral nicotine reduces the nigrostriatal neuronal loss observed in chemically induced PD (384, 385). PubMed:19126755

Appears in Networks:
Annotations
MeSH
Parkinson Disease
Text Location
Review

a(CHEBI:nicotine) decreases bp(GO:"neuron death") View Subject | View Object

However, in rodent and nonprimate animal models, nicotine has been shown to enhance striatal dopamine release and to prevent toxin-induced degeneration of dopaminergic neurons (384, 385). PubMed:19126755

Appears in Networks:
Annotations
MeSH
Corpus Striatum
Text Location
Review

path(MESH:"Alzheimer Disease") increases bp(GO:"neuron death") View Subject | View Object

AD also involves loss of neurons, beginning in the entorhinal cortex and later spreading to the neocortex (Braak et al., 2006); early in the disease, nicotinic acetylcholine receptors (nAChRs) are lost (Kadir et al., 2006). PubMed:19293145

Appears in Networks:
Annotations
MeSH
Entorhinal Cortex
MeSH
Neocortex

path(MESH:"Alzheimer Disease") positiveCorrelation bp(GO:"neuron death") View Subject | View Object

The most well-appreciated neuronal loss, however, is in the cholinergic system (155, 156), particularly the basal forebrain cholinergic system comprised of the medial septal nucleus, the horizontal and vertical diagonal bands of Broca, and the nucleus basalis of Meynert (157). PubMed:17009926

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

path(MESH:"Alzheimer Disease") positiveCorrelation bp(GO:"neuron death") View Subject | View Object

As AD worsens, cholinergic neurons are progressively lost and the number of nAChRs declines, particularly in the hippocampus and cortex (140, 158). PubMed:17009926

Appears in Networks:
Annotations
Cell Ontology (CL)
cholinergic neuron
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Alzheimer Disease

path(MESH:"Alzheimer Disease") increases bp(GO:"neuron death") View Subject | View Object

Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder afflicting millions of people. It is diagnosed by the progressive loss of cognitive function and behavioral defi cits and is characterized by the presence of neurofibrillary tangles (NFTs), senile plaques, cholinergic neuron loss, and neuronal atrophy at autopsy PubMed:24590577

Appears in Networks:

path(MESH:"Alzheimer Disease") positiveCorrelation bp(GO:"neuron death") View Subject | View Object

Dementia is a debilitating condition frequent in ageing populations, and Alzheimer's Disease (AD) accounts for 70% of all dementia cases. AD is characterized by neuropathological hallmarks consisting of an accumulation of Amyloid beta peptide (Ab) in extracellular plaques, intracellular deposits of tau protein, neuronal loss and, more recently, a prominent synaptic loss was identified (Braak and Braak,1991; Masliah et al., 2001; Selkoe,1991; Spires-Jones and Hyman, 2014) PubMed:25514383

Appears in Networks:

a(HBP:HBP00022) increases bp(GO:"neuron death") View Subject | View Object

It has been postulated that soluble or small oligomeric forms of Ab have deleterious effects in the brain, inducing impaired synaptic function and promoting neuronal degeneration [5]. PubMed:21718217

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Annotations
Confidence
High

a(HBP:HBP00074) increases bp(GO:"neuron death") View Subject | View Object

It has been postulated that soluble or small oligomeric forms of Ab have deleterious effects in the brain, inducing impaired synaptic function and promoting neuronal degeneration [5]. PubMed:21718217

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Annotations
Confidence
High

complex(a(CHEBI:"amyloid-beta"), p(HGNC:CHRNA7)) increases bp(GO:"neuron death") View Subject | View Object

Another important event that associates well with the Alzheimer disease pathology is the aggregation of the β-amyloid peptide [53]. This peptide interacts with α7 AChRs and has been reported to affect the nor- mal functioning of the latter, causing reduced neuronal survival [146,192–194]. PubMed:22040696

Appears in Networks:
Annotations
MeSH
Hippocampus

bp(GO:"phosphatidylinositol 3-kinase signaling") decreases bp(GO:"neuron death") View Subject | View Object

Recent studies have also demonstrated the importance of the phos- phatidylinositol 3-kinase (PI3K) pathway downstream of AChRs in pro- tecting neurons from death and up-regulating these receptors [148]. PubMed:22040696

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act(p(FPLX:PI3K)) decreases bp(GO:"neuron death") View Subject | View Object

Specifically, it has been shown that upon stimulation, α7 AChR activates PI3K via direct association with non-receptor type tyrosine kinase FYN and Janus-activated kinase 2 (JAK2), promoting the survival of neuronal cells (Fig. 3). PubMed:22040696

Appears in Networks:

path(MESH:"Alzheimer Disease") increases bp(GO:"neuron death") View Subject | View Object

Reduction of α7 AChRs in the CNS is linked with Alzheimer dis- ease, which has been shown to lead to neuronal loss [53,188–190]. PubMed:22040696

Appears in Networks:
Annotations
MeSH
Central Nervous System

a(HBP:"alpha-7-containing nAChR") association bp(GO:"neuron death") View Subject | View Object

For example, Bgt-sensitive a7-nAChRs have been implicated in processes such as vicinal control of neurotransmitter release [7,14], development and maintenance of neurites and synapses [18–20], long-term potentiation [95,96], seizures [97], and neuronal viability/death [21–24]. These intriguing findings underscore the need for further characterization of functional a7-nAChRs. PubMed:21787755

Appears in Networks:

path(MESH:"Amyotrophic Lateral Sclerosis") increases bp(GO:"neuron death") View Subject | View Object

There are different forms of amyotrophic lateral sclerosis (ALS), all primarily display widespread death of brainstem and spinal motoneurons, corticospinal degeneration, paralysis of skeletal muscle, and eventual neuronal cell death PubMed:14556719

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path(MESH:"Parkinson Disease") positiveCorrelation bp(GO:"neuron death") View Subject | View Object

In PD, the main neuropathological feature is the progressive death of neurons in the substantia nigra pars compacta with resulting loss of dopaminergic innervation of the striatum. PubMed:14556719

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Annotations
MeSH
Pars Compacta

path(MESH:"Prion Diseases") increases bp(GO:"neuron death") View Subject | View Object

Prion disease neuropathology is characterized by widespread neuronal death, accompanied by spongiform vacuolation and astrogliosis, usually combined with widespread deposits of extracellular amyloid aggregates. PubMed:14556719

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a(HBP:HBP00095) increases bp(GO:"neuron death") View Subject | View Object

Prefibrillar oligomeric α -syn has been proposed to contribute to neurodegeneration by perturbing cellular ion homeostasis20, by seeding the assembly of soluble α -syn into higher molecular weight aggregates21, and/or by imbalancing cellular proteostasis22,23. PubMed:27075649

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Lewy Bodies

composite(a(CHEBI:rotenone), p(HGNC:MAPT, var("p.Ala152Thr"))) causesNoChange bp(GO:"neuron death") View Subject | View Object

When measuring cell viability using the MTT assay, we found that patient-specific neurons are more sensitive than control neurons to cell death induced by rapamycin (Figure 3B) but not by staurosporine or rotenone (Figures S3B and S3C), suggesting compromised function in the mTOR pathway or related molecular pathways PubMed:27594586

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MAPT, var("p.Ala152Thr")) increases bp(GO:"neuron death") View Subject | View Object

We found that, indeed, TUJ1+ neurons showed reduced survival as measured by TUNEL analysis (Figure 3A) PubMed:27594586

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

composite(a(CHEBI:sirolimus), p(HGNC:MAPT, var("p.Ala152Thr"))) increases bp(GO:"neuron death") View Subject | View Object

When measuring cell viability using the MTT assay, we found that patient-specific neurons are more sensitive than control neurons to cell death induced by rapamycin (Figure 3B) but not by staurosporine or rotenone (Figures S3B and S3C), suggesting compromised function in the mTOR pathway or related molecular pathways PubMed:27594586

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

composite(a(CHEBI:staurosporine), p(HGNC:MAPT, var("p.Ala152Thr"))) causesNoChange bp(GO:"neuron death") View Subject | View Object

When measuring cell viability using the MTT assay, we found that patient-specific neurons are more sensitive than control neurons to cell death induced by rapamycin (Figure 3B) but not by staurosporine or rotenone (Figures S3B and S3C), suggesting compromised function in the mTOR pathway or related molecular pathways PubMed:27594586

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

g(DBSNP:rs63751011) increases bp(GO:"neuron death") View Subject | View Object

We found that, indeed, TUJ1+ neurons showed reduced survival as measured by TUNEL analysis (Figure 3A) PubMed:27594586

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

act(p(HGNC:MMP2)) increases bp(GO:"neuron death") View Subject | View Object

To examine the contributions of increased MMP-9 and MMP-2 to neuronal cell death, we used two compounds that are known to inhibit MMP-9 and MMP-2 activity (catalog #444278 and #444244, Calbiochem). We found that this treatment partially rescued the increased sensitivity to rapamycin and improved survival (Figure 3B) PubMed:27594586

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MMP2) increases bp(GO:"neuron death") View Subject | View Object

MMP-2 and MMP-9 seem to induce cell death directly, since this treatment also increased the TUNEL signal in iPSC-derived neurons (Figures S3D and S3E) PubMed:27594586

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

act(p(HGNC:MMP9)) increases bp(GO:"neuron death") View Subject | View Object

To examine the contributions of increased MMP-9 and MMP-2 to neuronal cell death, we used two compounds that are known to inhibit MMP-9 and MMP-2 activity (catalog #444278 and #444244, Calbiochem). We found that this treatment partially rescued the increased sensitivity to rapamycin and improved survival (Figure 3B) PubMed:27594586

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

p(HGNC:MMP9) increases bp(GO:"neuron death") View Subject | View Object

MMP-2 and MMP-9 seem to induce cell death directly, since this treatment also increased the TUNEL signal in iPSC-derived neurons (Figures S3D and S3E) PubMed:27594586

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Cerebral Cortex
MeSH
Neurons
MeSH
Frontotemporal Dementia

a(CHEBI:metformin) decreases bp(GO:"neuron death") View Subject | View Object

Moreover, reductions in levels of hyper phosphorylated tau and Aβ were seen in metformin- treated neurons 117,118 , while it blunted neuronal loss in a neurochemical lesion model of PD in mice 119 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Parkinson Disease

bp(MESH:Autophagy) negativeCorrelation bp(GO:"neuron death") View Subject | View Object

In a mouse model expressing the FTDP-17 mutant P301S, promoting autophagy with trehalose treatment beginning at weaning significantly reduced insoluble tau, as well as tau phosphorylated at T212/S214 (AT100) (97). However, no other phosphorylation sites were assessed. This effect was correlated with improved neuronal survival in cortical layers I–III (97). PubMed:24027553

Appears in Networks:
Annotations
MeSH
Frontotemporal Dementia
Text Location
Review

path(MESH:Tauopathies) positiveCorrelation bp(GO:"neuron death") View Subject | View Object

For example, tau pathology closely correlates to neuron loss and cognitive deficits PubMed:21882945

Appears in Networks:

bp(GO:"cellular senescence") increases bp(GO:"neuron death") View Subject | View Object

Tau transgenic mice with late stage pathology were treated with senolytics to remove senescent cells. Despite the advanced age and disease progression, MRI brain imaging and histopathological analyses indicated a reduction in total NFT density, neuron loss and ventricular enlargement PubMed:30126037

Appears in Networks:
Annotations
Confidence
High
MeSH
Alzheimer Disease

p(HGNC:MAPT) increases bp(GO:"neuron death") View Subject | View Object

Tau may be endocytosed, promoting an increase in intracellular calcium that results in neuronal death PubMed:28420982

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Exosomes
MeSH
Alzheimer Disease

path(MESH:"Alzheimer Disease") positiveCorrelation bp(GO:"neuron death") View Subject | View Object

Compared to non-demented controls, AD brains exhibit up to 50% of neuronal loss in the cortex, exceeding the number of NFTs (Gómez-Isla et al., 1997) PubMed:28420982

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex

path(MESH:Tauopathies) association bp(GO:"neuron death") View Subject | View Object

In AD, tau pathology and neuronal cell loss coincide in the same brain regions, and as brain dysfunction progresses, NFTs are found in greater anatomical distributions (Ihara, 2001) PubMed:28420982

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Annotations
Confidence
High

p(MGI:Ttbk1) increases bp(GO:"neuron death") View Subject | View Object

Overexpression of TTBK1 was sufficient in inducing spatial learning impairment in mice, which is associated with enhanced Cdk5 activity and reduction in cell surface level of NR2B. Over-expressionof TTBK1 transgene in JNPL3 mice resulted in accumulation of pre-tangle forms of tau. Inaddition, TTBK1 expression plays a unique role in accelerating motor neuron degeneration and neuroinflammation in JNPL3mice. PubMed:24808823

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act(p(HGNC:CASP3)) increases bp(GO:"neuron death") View Subject | View Object

NO can also bring about apoptosis of hippocampal neurons via caspase- 3 activity [50] whereas astrocyte-secreted IL-1 beta can increase the production of APP and A beta from neu- rons [51–53] (Fig. 1). PubMed:27314526

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Hippocampus
MeSH
Alzheimer Disease
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Caspase subgraph
NeuroMMSigDB
Interleukin signaling subgraph
NeuroMMSigDB
Nitric oxide subgraph

complex(p(HGNC:APP), p(HGNC:HSD17B10)) increases bp(GO:"neuron death") View Subject | View Object

Neurons from these animals exhibited increased oxidative stress, increased generation of ROS, DNA fragmentation, neuronal apoptosis, and impairment in learning, compared to single-transgenic mAPP mice. PubMed:30444369

Appears in Networks:
Annotations
MeSH
Neurons

p(HGNC:SH3GL2) association bp(GO:"neuron death") View Subject | View Object

This results in the activation of mitogen-activated protein kinase kinase kinase 1 (MAP3K1), 114 which then activates a cascade of kinases that eventually leads to the translocation of JNK to the nucleus or other target sites to phosphorylate downstream effectors, thereby affecting significant aspects of neuronal function such as neurite outgrowth, mitochondrial function, synaptic plasticity and apoptosis. 1 PubMed:30444369

Appears in Networks:
Annotations
MeSH
Neurons

act(complex(GO:"protein phosphatase type 2A complex")) decreases bp(GO:"neuron death") View Subject | View Object

Not surprisingly, inhibition of total cellular PP2A activity ultimately leads to neuronal cell death. PubMed:24653673

Appears in Networks:

bp(GO:proteolysis) decreases bp(GO:"neuron death") View Subject | View Object

With neurons profoundly relying on macroautophagy for clearance of toxic protein aggregates, impairment in the proteolytic systems ultimately results in progressive neuronal death, a common feature in several neurodegenerative diseases [27]. PubMed:29758300

Appears in Networks:

deg(p(HGNC:MAPT, pmod(Ph))) decreases bp(GO:"neuron death") View Subject | View Object

TFEB has been shown to effectively clear phosphorylated tau proteins through A-LS, resulting in ameliorated neuronal loss and neuroinflammation, as well as improved cognitive performance [89]. PubMed:29758300

Appears in Networks:

path(MESH:"Neurodegenerative Diseases") association bp(GO:"neuron death") View Subject | View Object

With neurons profoundly relying on macroautophagy for clearance of toxic protein aggregates, impairment in the proteolytic systems ultimately results in progressive neuronal death, a common feature in several neurodegenerative diseases [27]. PubMed:29758300

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act(p(HGNC:RAB5A)) positiveCorrelation bp(GO:"neuron death") View Subject | View Object

Interactions between FAD-mutant forms of APP and APP binding protein (APP-BP1) on endosomes also initiate pathological rab5 activation, which was shown to promote a neuronal apoptosis cascade (Laifenfeld et al. 2007). PubMed:22908190

Appears in Networks:

p(HBP:"Tau isoform D (383 aa)", var("p.Pro301Leu")) increases bp(GO:"neuron death") View Subject | View Object

At the later stages, the mutant-tau lines showed microtubule loss and non-apoptotic neuronal death, paralleled by a complete loss of touch response (62). PubMed:29191965

Appears in Networks:

p(HBP:"Tau isoform D (383 aa)", var("p.Arg406Trp")) increases bp(GO:"neuron death") View Subject | View Object

At the later stages, the mutant-tau lines showed microtubule loss and non-apoptotic neuronal death, paralleled by a complete loss of touch response (62). PubMed:29191965

Appears in Networks:

path(MESH:"Alzheimer Disease") positiveCorrelation bp(GO:"neuron death") View Subject | View Object

In brains of individuals with AD, neuron loss in the superior temporal sulcus region exceeds the number of NFTs more than sevenfold, implying that the majority of neurons probably die without having developed NFTs PubMed:26631930

Appears in Networks:

g(HGNC:MIR22) decreases bp(GO:"neuron death") View Subject | View Object

For example, miR‐22 with its neuroprotective function prevents the death of neurons by apoptosis. PubMed:30663117

Appears in Networks:
Annotations
MeSH
Huntington Disease

p(HGNC:LRRK2, var("?")) increases bp(GO:"neuron death") View Subject | View Object

The expression of LRRK2 mutants can cause apoptosis of neuronal and neuroblastoma cells PubMed:30663117

Appears in Networks:
Annotations
MeSH
Parkinson Disease

p(HGNC:PARK7) decreases bp(GO:"neuron death") View Subject | View Object

It also inhibits apoptosis and prevents the death of neuron PubMed:30663117

Appears in Networks:
Annotations
MeSH
Parkinson Disease

act(a(MESH:Microglia)) increases bp(GO:"neuron death") View Subject | View Object

Amyloid-β also induces microglial activation that results in NF-κB – induced expression of pro-inflammatory cytokines such as TNFα, IL1β, IL6, and IL8 from the microglia resulting in neuronal death PubMed:28745240

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

act(complex(GO:"NF-kappaB complex")) decreases bp(GO:"neuron death") View Subject | View Object

Consequently, NF-κB is constitutively activated in the excitatory neurons of the cerebral cortex (layers 2, 4, and 5), hippocampus (granule and pyramidal neurons of CA1 and CA3), and cerebellar granule cells and this constitutive activity is indispensable for neuronal survival in response to glutamate-induced excitotoxicity PubMed:28745240

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

complex(GO:"NF-kappaB complex") decreases bp(GO:"neuron death") View Subject | View Object

Preponderance of evidence has implicated NF-κB as a survival factor in neurons [24, 114, 115] primarily because of the ability of NF-κB to suppress apoptosis in response to excitotoxic and apoptotic stimuli PubMed:28745240

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

complex(GO:"NF-kappaB complex") decreases bp(GO:"neuron death") View Subject | View Object

Inhibition of NF-κB activity using a κB decoy DNA that results in the sequestration of NF-κB, increases the susceptibility of hippocampal neurons to noxious and apoptotic stimuli PubMed:28745240

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Alzheimer Disease

act(complex(GO:"NF-kappaB complex")) decreases bp(GO:"neuron death") View Subject | View Object

NF-κB activation also protects hippocampal neurons from oxidative stress-induced apoptosis by inducing manganese superoxide dismutase (MnSOD) expression and mitigating peroxynitrite-induced protein nitration PubMed:28745240

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Alzheimer Disease

p(HGNC:CXCL8) increases bp(GO:"neuron death") View Subject | View Object

Amyloid-β also induces microglial activation that results in NF-κB – induced expression of pro-inflammatory cytokines such as TNFα, IL1β, IL6, and IL8 from the microglia resulting in neuronal death PubMed:28745240

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Alzheimer Disease

p(HGNC:IL1B) increases bp(GO:"neuron death") View Subject | View Object

Amyloid-β also induces microglial activation that results in NF-κB – induced expression of pro-inflammatory cytokines such as TNFα, IL1β, IL6, and IL8 from the microglia resulting in neuronal death PubMed:28745240

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Alzheimer Disease

p(HGNC:IL6) increases bp(GO:"neuron death") View Subject | View Object

Amyloid-β also induces microglial activation that results in NF-κB – induced expression of pro-inflammatory cytokines such as TNFα, IL1β, IL6, and IL8 from the microglia resulting in neuronal death PubMed:28745240

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Alzheimer Disease

p(HGNC:TNF) increases bp(GO:"neuron death") View Subject | View Object

Amyloid-β also induces microglial activation that results in NF-κB – induced expression of pro-inflammatory cytokines such as TNFα, IL1β, IL6, and IL8 from the microglia resulting in neuronal death PubMed:28745240

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Alzheimer Disease

path(HBP:Excitotoxicity) increases bp(GO:"neuron death") View Subject | View Object

Consequently, NF-κB is constitutively activated in the excitatory neurons of the cerebral cortex (layers 2, 4, and 5), hippocampus (granule and pyramidal neurons of CA1 and CA3), and cerebellar granule cells and this constitutive activity is indispensable for neuronal survival in response to glutamate-induced excitotoxicity PubMed:28745240

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Alzheimer Disease

a(CHEBI:"N(5)-ethyl-L-glutamine") decreases bp(GO:"neuron death") View Subject | View Object

Moreover, the level of A 1-42 was lowered by L-theanine and caused A 1-42- activated neuronal cell death in the cortex and hip-pocampus of the brain [128]. PubMed:29179999

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Cerebral Cortex
MeSH
Hippocampus

a(CHEBI:"amyloid-beta polypeptide 42") increases bp(GO:"neuron death") View Subject | View Object

Moreover, the level of A 1-42 was lowered by L-theanine and caused A 1-42- activated neuronal cell death in the cortex and hip-pocampus of the brain [128]. PubMed:29179999

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Cerebral Cortex
MeSH
Hippocampus

a(PUBCHEM:164676) decreases bp(GO:"neuron death") View Subject | View Object

Moreover, tanshinone IIA inhibited apoptosis in A 25-35-induced cells [232] and exerted anti-inflammatory activity in atherosclerosis and neuroprotective activity in cerebral ischemia/reperfusion impairment [233,234] PubMed:29179999

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Brain Ischemia

a(PUBCHEM:24721561) decreases bp(GO:"neuron death") View Subject | View Object

Ginsenoside Rd showed neuro-protective effects with A 40 activated impairments in rat brains [225] and ameliorated learning and memory capability in APP transgenic mice, via reducing the activity of NF-B [226]. PubMed:29179999

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Brain
MeSH
Alzheimer Disease

a(CHEBI:"amyloid-beta") increases bp(GO:"neuron death") View Subject | View Object

Mechanistically, the Aβ induced neuronal apoptosis has been attributed to the increase in the ratio of proapoptotic gene (BAX) transcription to that of the anti-apoptotic gene Bcl-Xl, and/or to the reduction in constitutively activated NF-κB with consequent increase in the cytoplasmic IκB proteins PubMed:25652642

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Alzheimer Disease

act(complex(GO:"NF-kappaB complex")) decreases bp(GO:"neuron death") View Subject | View Object

Cell death is preceded by reduction in the NF-κB regulated transcription of anti-apoptotic genes suggesting that a minimal threshold of NF-κB activity is needed for neuronal survival PubMed:25652642

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a(PUBCHEM:9832404) decreases bp(GO:"neuron death") View Subject | View Object

On the other hand, chronic treatment with an eight-amino-acid peptide snippet from ADNP (NAP), also known as davunetide, restored both Beclin1 and ADNP mRNA levels along with ADNP-LC3 interaction, thus providing neuroprotection while ameliorating schizophrenic-like behavioral and cognitive deficits in Map6+/- mice PubMed:30061532

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Schizophrenia

Out-Edges 17

bp(GO:"neuron death") positiveCorrelation a(HBP:HBP00074) View Subject | View Object

In addition, the load of AβO deposits significantly correlated with fibrillar Aβ plaque deposition as well as with neuronal loss and numbers of astrocytes, although not with memory deficits. PubMed:29196815

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Extracellular Space
Cell Ontology (CL)
neuron
Confidence
High

bp(GO:"neuron death") association complex(a(HBP:HBP00042), p(HGNC:TNFRSF21)) View Subject | View Object

Although sAPPbeta only differs from sAPPalpha by lacking the Abeta1-16 region at its carboxyl-terminus, sAPPbeta was reported to function as a death receptor 6 ligand and mediate axonal pruning and neuronal cell death [94] PubMed:21214928

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Endosomes
Confidence
High
MeSH
Neurons

bp(GO:"neuron death") association path(MESH:"Alzheimer Disease") View Subject | View Object

Plaques consisting of beta-amyloid (Abeta) peptide (Selkoe 1998), neurofibrillary tangles consisting largely of hyperphosphorylated microtubule-associated tau protein (Buee et al. 2000; Gendron and Petrucelli 2009) and neuron loss in the hippocampus and cortex regions are the major pathological hallmarks of Alzheimer’s disease. PubMed:22122372

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Confidence
High
MeSH
Cerebral Cortex
MeSH
Hippocampus

bp(GO:"neuron death") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

The most well-appreciated neuronal loss, however, is in the cholinergic system (155, 156), particularly the basal forebrain cholinergic system comprised of the medial septal nucleus, the horizontal and vertical diagonal bands of Broca, and the nucleus basalis of Meynert (157). PubMed:17009926

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Cell Ontology (CL)
cholinergic neuron
MeSH
Alzheimer Disease

bp(GO:"neuron death") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

As AD worsens, cholinergic neurons are progressively lost and the number of nAChRs declines, particularly in the hippocampus and cortex (140, 158). PubMed:17009926

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Cell Ontology (CL)
cholinergic neuron
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Alzheimer Disease

bp(GO:"neuron death") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Dementia is a debilitating condition frequent in ageing populations, and Alzheimer's Disease (AD) accounts for 70% of all dementia cases. AD is characterized by neuropathological hallmarks consisting of an accumulation of Amyloid beta peptide (Ab) in extracellular plaques, intracellular deposits of tau protein, neuronal loss and, more recently, a prominent synaptic loss was identified (Braak and Braak,1991; Masliah et al., 2001; Selkoe,1991; Spires-Jones and Hyman, 2014) PubMed:25514383

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bp(GO:"neuron death") association a(HBP:"alpha-7-containing nAChR") View Subject | View Object

For example, Bgt-sensitive a7-nAChRs have been implicated in processes such as vicinal control of neurotransmitter release [7,14], development and maintenance of neurites and synapses [18–20], long-term potentiation [95,96], seizures [97], and neuronal viability/death [21–24]. These intriguing findings underscore the need for further characterization of functional a7-nAChRs. PubMed:21787755

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bp(GO:"neuron death") positiveCorrelation path(MESH:"Parkinson Disease") View Subject | View Object

In PD, the main neuropathological feature is the progressive death of neurons in the substantia nigra pars compacta with resulting loss of dopaminergic innervation of the striatum. PubMed:14556719

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Pars Compacta

bp(GO:"neuron death") negativeCorrelation bp(MESH:Autophagy) View Subject | View Object

In a mouse model expressing the FTDP-17 mutant P301S, promoting autophagy with trehalose treatment beginning at weaning significantly reduced insoluble tau, as well as tau phosphorylated at T212/S214 (AT100) (97). However, no other phosphorylation sites were assessed. This effect was correlated with improved neuronal survival in cortical layers I–III (97). PubMed:24027553

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Frontotemporal Dementia
Text Location
Review

bp(GO:"neuron death") positiveCorrelation path(MESH:Tauopathies) View Subject | View Object

For example, tau pathology closely correlates to neuron loss and cognitive deficits PubMed:21882945

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bp(GO:"neuron death") association path(MESH:Tauopathies) View Subject | View Object

In AD, tau pathology and neuronal cell loss coincide in the same brain regions, and as brain dysfunction progresses, NFTs are found in greater anatomical distributions (Ihara, 2001) PubMed:28420982

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Confidence
High

bp(GO:"neuron death") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Compared to non-demented controls, AD brains exhibit up to 50% of neuronal loss in the cortex, exceeding the number of NFTs (Gómez-Isla et al., 1997) PubMed:28420982

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Confidence
Medium
MeSH
Cerebral Cortex

bp(GO:"neuron death") association p(HGNC:SH3GL2) View Subject | View Object

This results in the activation of mitogen-activated protein kinase kinase kinase 1 (MAP3K1), 114 which then activates a cascade of kinases that eventually leads to the translocation of JNK to the nucleus or other target sites to phosphorylate downstream effectors, thereby affecting significant aspects of neuronal function such as neurite outgrowth, mitochondrial function, synaptic plasticity and apoptosis. 1 PubMed:30444369

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Neurons

bp(GO:"neuron death") association path(MESH:"Neurodegenerative Diseases") View Subject | View Object

With neurons profoundly relying on macroautophagy for clearance of toxic protein aggregates, impairment in the proteolytic systems ultimately results in progressive neuronal death, a common feature in several neurodegenerative diseases [27]. PubMed:29758300

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bp(GO:"neuron death") positiveCorrelation act(p(HGNC:RAB5A)) View Subject | View Object

Interactions between FAD-mutant forms of APP and APP binding protein (APP-BP1) on endosomes also initiate pathological rab5 activation, which was shown to promote a neuronal apoptosis cascade (Laifenfeld et al. 2007). PubMed:22908190

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bp(GO:"neuron death") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

In brains of individuals with AD, neuron loss in the superior temporal sulcus region exceeds the number of NFTs more than sevenfold, implying that the majority of neurons probably die without having developed NFTs PubMed:26631930

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bp(GO:"neuron death") increases g(MGI:Ebf3) View Subject | View Object

For example, EBF3‐AS is a lncRNA that increases significantly in the hippocampus of the mice whose neurons had undergone apoptosis (Figure 1) PubMed:30663117

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MeSH
Hippocampus
MeSH
Alzheimer Disease

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.