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path(MESH:"Amyotrophic Lateral Sclerosis")

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Entity

Name
Amyotrophic Lateral Sclerosis
Namespace
mesh
Namespace Version
20181007
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/8ccfed235e418e4c8aa576f9a5ef0f838e794c7f/external/mesh-names.belns

Appears in Networks 8

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

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

The Biology of Proteostasis in Aging and Disease v1.0.0

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

Oxidative stress in health and disease: The therapeutic potential of Nrf2 activation v1.0.0

Axonal Transport, Tau Protein, and Neurodegeneration 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

In-Edges 15

a(MESH:"Cholinergic Neurons") negativeCorrelation path(MESH:"Amyotrophic Lateral Sclerosis") View Subject | View Object

Further highlighting the importance of the cholinergic system in the CNS, cholinergic neuronal loss, especially in the basal forebrain, occurs not only in AD, but also in Parkinson’s disease [190, 191], Down syndrome [192], amyotrophic lateral sclerosis [193, 194], progressive supranuclear palsy [195, 196], and olivopontocerebellar atrophy [197] PubMed:26813123

Appears in Networks:
Annotations
MeSH
Basal Forebrain
MeSH
Central Nervous System

p(HGNC:SOD1, var("?")) association path(MESH:"Amyotrophic Lateral Sclerosis") View Subject | View Object

There is very little evidence to suggest that alterations in SOD are a common feature of sporadic ALS (Alexander et al., 2002). PubMed:14556719

Appears in Networks:

p(HGNC:UBL5) positiveCorrelation path(MESH:"Amyotrophic Lateral Sclerosis") View Subject | View Object

Spinal cords from sporadic ALS cases also express increased levels of the gene for ubiquitin-like protein 5. PubMed:14556719

Appears in Networks:
Annotations
MeSH
Spinal Cord

a(CHEBI:sirolimus) decreases path(MESH:"Amyotrophic Lateral Sclerosis") View Subject | View Object

Treatment of cell, Drosophila, and mouse models of HD, SCA3/MJD, AD, PD, and ALS with the mTOR inhibitor rapamycin (or a derivative) reduces aggregation and suppresses disease (140– 143). PubMed:25784053

Appears in Networks:
Annotations
Cell Ontology (CL)
motor neuron

p(HGNC:ATF6) negativeCorrelation path(MESH:"Amyotrophic Lateral Sclerosis") View Subject | View Object

Disruption of the ATF6 arm of the UPR(ER) is reported to occur in mouse models of HD and a VAPB cell model of ALS, suggesting that differential changes in UPR arms may be a feature of disease progression (102, 103). PubMed:25784053

Appears in Networks:
Annotations
Cell Ontology (CL)
motor neuron

p(HGNC:CHMP2B) association path(MESH:"Amyotrophic Lateral Sclerosis") View Subject | View Object

ALS shares many causal genes with FTD, including SQSTM1, CHMP2B, TBK1 (which encodes tank-binding kinase 1), OPTN (which encodes optineurin) and other genes associated with deficits in ALN and mitophagy. PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Amyotrophic Lateral Sclerosis

p(HGNC:OPTN) association path(MESH:"Amyotrophic Lateral Sclerosis") View Subject | View Object

ALS shares many causal genes with FTD, including SQSTM1, CHMP2B, TBK1 (which encodes tank-binding kinase 1), OPTN (which encodes optineurin) and other genes associated with deficits in ALN and mitophagy. PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Amyotrophic Lateral Sclerosis

p(HGNC:SQSTM1) association path(MESH:"Amyotrophic Lateral Sclerosis") View Subject | View Object

ALS shares many causal genes with FTD, including SQSTM1, CHMP2B, TBK1 (which encodes tank-binding kinase 1), OPTN (which encodes optineurin) and other genes associated with deficits in ALN and mitophagy. PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Amyotrophic Lateral Sclerosis

p(HGNC:TBK1) association path(MESH:"Amyotrophic Lateral Sclerosis") View Subject | View Object

ALS shares many causal genes with FTD, including SQSTM1, CHMP2B, TBK1 (which encodes tank-binding kinase 1), OPTN (which encodes optineurin) and other genes associated with deficits in ALN and mitophagy. PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Amyotrophic Lateral Sclerosis

a(HBP:"protein aggregates") positiveCorrelation path(MESH:"Amyotrophic Lateral Sclerosis") View Subject | View Object

Overexpression of the HSPB8-BAG3 complex also stimulates autophagy and facilitates the clearance of mutated aggregation-prone proteins, the accumulation of which characterizes many neurodegenerative disorders such as Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis (Seidel et al., 2011). PubMed:22020111

Appears in Networks:

a(MESH:"Intermediate Filaments") positiveCorrelation path(MESH:"Amyotrophic Lateral Sclerosis") View Subject | View Object

. In ALS, accumulation of NFs is a prominent feature (Rouleau et al., 1996), and it has been demonstrated that NFs contribute heavily to the axonopathy of tau transgenic mice (Ishihara et al., 2001a). PubMed:12428809

Appears in Networks:

bp(GO:macroautophagy) negativeCorrelation path(MESH:"Amyotrophic Lateral Sclerosis") View Subject | View Object

Finally, numerous studies using iPSC models have implicated changes in macroautophagy pathways in Parkinson’s disease [137–144], Gaucher disease [145], Niemann-Pick Type C1 disease [146–148] and diseases affecting motor neurons, including ALS [149,150], spinal and bulbar muscular atrophy (SBMA) [151], Brown- Vialetto disease [152], Charcot-Marie-Tooth 2A [153] and hereditary spastic paraplegia [154] PubMed:29758300

Appears in Networks:

p(HGNC:TARDBP, pmod(HBP:misfolding)) positiveCorrelation path(MESH:"Amyotrophic Lateral Sclerosis") View Subject | View Object

Another common proteinopathy occurs from the misfolding of TARDNA binding protein 43 kDa (TDP-43), which is primarily seen in amyotrophic lateral sclerosis (ALS) and FTD [67] PubMed:29758300

Appears in Networks:

p(HGNC:TARDBP, pmod(Ub)) positiveCorrelation path(MESH:"Amyotrophic Lateral Sclerosis") View Subject | View Object

In this regard, the entity of frontotemporal lobar degeneration (FTLD) with Ub-positive/tau-negative inclusions was described later, and TDP43 was identified as the ubiquitinated protein in both this disorder and ALS (Neuman et al. 2006). PubMed:22908190

Appears in Networks:

p(HGNC:TARDBP, pmod(Ub)) positiveCorrelation path(MESH:"Amyotrophic Lateral Sclerosis") View Subject | View Object

In AD, tau is ubiquitinated, in Parkinson’s disease and dementia with Lewy bodies, it is a-synuclein, and in ALS and FTLD-U, it is TDP-43 PubMed:22908190

Appears in Networks:

Out-Edges 21

path(MESH:"Amyotrophic Lateral Sclerosis") negativeCorrelation a(MESH:"Cholinergic Neurons") View Subject | View Object

Further highlighting the importance of the cholinergic system in the CNS, cholinergic neuronal loss, especially in the basal forebrain, occurs not only in AD, but also in Parkinson’s disease [190, 191], Down syndrome [192], amyotrophic lateral sclerosis [193, 194], progressive supranuclear palsy [195, 196], and olivopontocerebellar atrophy [197] PubMed:26813123

Appears in Networks:
Annotations
MeSH
Basal Forebrain
MeSH
Central Nervous System

path(MESH:"Amyotrophic Lateral Sclerosis") decreases a(MESH:"Brain Stem") 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

Appears in Networks:

path(MESH:"Amyotrophic Lateral Sclerosis") decreases bp(GO:"spinal cord development") 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

Appears in Networks:

path(MESH:"Amyotrophic Lateral Sclerosis") decreases a(MESH:"Pyramidal Tracts") 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

Appears in Networks:

path(MESH:"Amyotrophic Lateral Sclerosis") increases path(MESH:Paralysis) 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

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

Appears in Networks:

path(MESH:"Amyotrophic Lateral Sclerosis") association p(HGNC:SOD1, var("?")) View Subject | View Object

There is very little evidence to suggest that alterations in SOD are a common feature of sporadic ALS (Alexander et al., 2002). PubMed:14556719

Appears in Networks:

path(MESH:"Amyotrophic Lateral Sclerosis") increases p(HGNC:RNF19A) View Subject | View Object

Interestingly, dorfin expression is increased in the spinal cord of ALS patients (Ishigaki et al., 2002), which may suggest that the expression of the E3 ligase is increased in an attempt to enhance clearance of the mutant SOD1. PubMed:14556719

Appears in Networks:

path(MESH:"Amyotrophic Lateral Sclerosis") positiveCorrelation p(HGNC:UBL5) View Subject | View Object

Spinal cords from sporadic ALS cases also express increased levels of the gene for ubiquitin-like protein 5. PubMed:14556719

Appears in Networks:
Annotations
MeSH
Spinal Cord

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

In contrast to findings in HD, AD, and PD, a recent study has suggested that autophagy is enhanced in ALS mice. PubMed:25784053

Appears in Networks:

path(MESH:"Amyotrophic Lateral Sclerosis") negativeCorrelation p(HGNC:ATF6) View Subject | View Object

Disruption of the ATF6 arm of the UPR(ER) is reported to occur in mouse models of HD and a VAPB cell model of ALS, suggesting that differential changes in UPR arms may be a feature of disease progression (102, 103). PubMed:25784053

Appears in Networks:
Annotations
Cell Ontology (CL)
motor neuron

path(MESH:"Amyotrophic Lateral Sclerosis") association p(HGNC:SQSTM1) View Subject | View Object

ALS shares many causal genes with FTD, including SQSTM1, CHMP2B, TBK1 (which encodes tank-binding kinase 1), OPTN (which encodes optineurin) and other genes associated with deficits in ALN and mitophagy. PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Amyotrophic Lateral Sclerosis

path(MESH:"Amyotrophic Lateral Sclerosis") association p(HGNC:CHMP2B) View Subject | View Object

ALS shares many causal genes with FTD, including SQSTM1, CHMP2B, TBK1 (which encodes tank-binding kinase 1), OPTN (which encodes optineurin) and other genes associated with deficits in ALN and mitophagy. PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Amyotrophic Lateral Sclerosis

path(MESH:"Amyotrophic Lateral Sclerosis") association p(HGNC:TBK1) View Subject | View Object

ALS shares many causal genes with FTD, including SQSTM1, CHMP2B, TBK1 (which encodes tank-binding kinase 1), OPTN (which encodes optineurin) and other genes associated with deficits in ALN and mitophagy. PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Amyotrophic Lateral Sclerosis

path(MESH:"Amyotrophic Lateral Sclerosis") association p(HGNC:OPTN) View Subject | View Object

ALS shares many causal genes with FTD, including SQSTM1, CHMP2B, TBK1 (which encodes tank-binding kinase 1), OPTN (which encodes optineurin) and other genes associated with deficits in ALN and mitophagy. PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Amyotrophic Lateral Sclerosis

path(MESH:"Amyotrophic Lateral Sclerosis") positiveCorrelation a(HBP:"protein aggregates") View Subject | View Object

Overexpression of the HSPB8-BAG3 complex also stimulates autophagy and facilitates the clearance of mutated aggregation-prone proteins, the accumulation of which characterizes many neurodegenerative disorders such as Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis (Seidel et al., 2011). PubMed:22020111

Appears in Networks:

path(MESH:"Amyotrophic Lateral Sclerosis") positiveCorrelation a(MESH:"Intermediate Filaments") View Subject | View Object

. In ALS, accumulation of NFs is a prominent feature (Rouleau et al., 1996), and it has been demonstrated that NFs contribute heavily to the axonopathy of tau transgenic mice (Ishihara et al., 2001a). PubMed:12428809

Appears in Networks:

path(MESH:"Amyotrophic Lateral Sclerosis") positiveCorrelation p(HGNC:TARDBP, pmod(HBP:misfolding)) View Subject | View Object

Another common proteinopathy occurs from the misfolding of TARDNA binding protein 43 kDa (TDP-43), which is primarily seen in amyotrophic lateral sclerosis (ALS) and FTD [67] PubMed:29758300

Appears in Networks:

path(MESH:"Amyotrophic Lateral Sclerosis") negativeCorrelation bp(GO:macroautophagy) View Subject | View Object

Finally, numerous studies using iPSC models have implicated changes in macroautophagy pathways in Parkinson’s disease [137–144], Gaucher disease [145], Niemann-Pick Type C1 disease [146–148] and diseases affecting motor neurons, including ALS [149,150], spinal and bulbar muscular atrophy (SBMA) [151], Brown- Vialetto disease [152], Charcot-Marie-Tooth 2A [153] and hereditary spastic paraplegia [154] PubMed:29758300

Appears in Networks:

path(MESH:"Amyotrophic Lateral Sclerosis") positiveCorrelation p(HGNC:TARDBP, pmod(Ub)) View Subject | View Object

In this regard, the entity of frontotemporal lobar degeneration (FTLD) with Ub-positive/tau-negative inclusions was described later, and TDP43 was identified as the ubiquitinated protein in both this disorder and ALS (Neuman et al. 2006). PubMed:22908190

Appears in Networks:

path(MESH:"Amyotrophic Lateral Sclerosis") positiveCorrelation p(HGNC:TARDBP, pmod(Ub)) View Subject | View Object

In AD, tau is ubiquitinated, in Parkinson’s disease and dementia with Lewy bodies, it is a-synuclein, and in ALS and FTLD-U, it is TDP-43 PubMed:22908190

Appears in Networks:

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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.