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a(GO:lysosome)

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Entity

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

Appears in Networks 9

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

Interplay of pathogenic forms of human tau with different autophagic pathways v1.0.1

Extracellular Monomeric and Aggregated Tau Efficiently Enter Human Neurons through Overlapping but Distinct Pathways v1.0.1

Clearance of Amyloid Beta and Tau in Alzheimer’s Disease:from Mechanisms to Therapy v1.0.1

Tau Modifications v1.9.5

Tau Modifications Sections of NESTOR

The role of inflammasome in Alzheimer’s disease v1.0.3

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

Autophagy and the ubiquitin-proteasome system: collaborators in neuroprotection v1.0.0

In-Edges 24

complex(a(GO:amphisome), a(GO:lysosome)) hasComponent a(GO:lysosome) View Subject | View Object

Appears in Networks:

g(HGNC:APP, var("?")) decreases act(a(GO:lysosome)) View Subject | View Object

Fifth, mutations in APP similarly disrupt endosomal and lysosomal func- tion, in part owing to accumulation of the β-secretase- generated, carboxy-terminal and Aβ42-containing fragment of APP called C99 (REF.66) . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

complex(a(GO:lysosome), p(MGI:Mapt)) hasComponent a(GO:lysosome) View Subject | View Object

Appears in Networks:

complex(a(GO:lysosome), p(MGI:Lrrk2, var("?"))) hasComponent a(GO:lysosome) View Subject | View Object

Appears in Networks:

complex(a(GO:lysosome), p(MGI:Mapt, var("p.Ala152Thr"))) hasComponent a(GO:lysosome) View Subject | View Object

Appears in Networks:

complex(a(GO:lysosome), p(MGI:Mapt, var("p.Pro301Leu"))) hasComponent a(GO:lysosome) View Subject | View Object

Appears in Networks:

complex(a(GO:lysosome), p(MGI:Snca, var("?"))) hasComponent a(GO:lysosome) View Subject | View Object

Appears in Networks:

a(HBP:"Tau aggregates") association a(GO:lysosome) View Subject | View Object

Monomeric and aggregated tau-Dylight were also detected in LAMP1+late endosomes and lysosomes, consistent with endocytosed proteins first reaching early endosomes, before late endosomes and lysosomes PubMed:29590627

Appears in Networks:

p(HGNC:MAPT, var("p.Pro301Ser")) association a(GO:lysosome) View Subject | View Object

Monomeric and aggregated tau-Dylight were also detected in LAMP1+late endosomes and lysosomes, consistent with endocytosed proteins first reaching early endosomes, before late endosomes and lysosomes PubMed:29590627

Appears in Networks:

p(HGNC:TFEB) increases act(a(GO:lysosome)) View Subject | View Object

Xiao et al. have also obtained the consistent conclusion that transcriptional factor EB, a master regulator of lysosome biogenesis, improves lysosomal function in astrocytes, which may promote Aβ clearance and attenuate plaque pathogenesis (Xiao et al. 2014) PubMed:29626319

Appears in Networks:
Annotations
MeSH
Astrocytes

p(HGNC:TFEB) increases act(a(GO:lysosome)) View Subject | View Object

For example, like Aβ, clearance of pTau/NFT also can be regulated by TFEB, which increases the activity of autophagy and lysosome (Polito et al. 2014) PubMed:29626319

Appears in Networks:

p(HGNC:SUMO1) partOf a(GO:lysosome) View Subject | View Object

Appears in Networks:

a(CHEBI:"amyloid-beta") decreases a(GO:lysosome) View Subject | View Object

Phagocytosis and subsequent lysosomal damage trigger by Aβ initiate the activation of the NLRP3 inflammasome in the microglia (Halle et al., 2008) PubMed:24561250

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell
Confidence
High
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Endosomal lysosomal subgraph

complex(p(HGNC:TFEB), p(INTERPRO:"cAMP response element binding (CREB) protein")) increases a(GO:lysosome) View Subject | View Object

Under starvation or stress, TFEB translocates to the nucleus and binds the CRE element to promote expression of macroautophagy and lysosomal genes [88]. PubMed:29758300

Appears in Networks:

p(HGNC:TFEB) regulates a(GO:lysosome) View Subject | View Object

Another modulator of A-LS implicated in AD pathology is transcription factor EB (TFEB), a master regulator of lysosome biogenesis PubMed:29758300

Appears in Networks:

p(HGNC:PSEN1, var("p.Ala246Glu")) decreases act(a(GO:lysosome)) View Subject | View Object

In a similar vein, PSEN1 A246E mutant cortical neurons have reduced mitophagy compared to control neurons, which is associated more with decreased lysosomal function rather than mitochondrial targeting [132]. PubMed:29758300

Appears in Networks:

path(MESH:"Alzheimer Disease") increases a(GO:lysosome) View Subject | View Object

Recently, a comprehensive investigation utilizing gene expression analysis of the hippocampal region (CA1) of patients with Alzheimer’s disease identified that autophagosome formation and lysosomal biogenesis genes were upregulated at early stages of AD [21] PubMed:29758300

Appears in Networks:
Annotations
MeSH
CA1 Region, Hippocampal

complex(a(GO:"late endosome"), a(GO:autophagosome), a(GO:lysosome)) hasComponent a(GO:lysosome) View Subject | View Object

Appears in Networks:

path(MESH:"Alzheimer Disease") positiveCorrelation a(GO:lysosome) View Subject | View Object

A continuum of pathological changes of the lysosomal network unfolds in neurons as Alzheimer disease progresses, including dysregulation of endocytosis, increased lysosome biogenesis and, later, progressive failure of lysosomal clearance mechanisms (Fig. 6; Nixon et al. 2006). PubMed:22908190

Appears in Networks:

path(MESH:"Alzheimer Disease") negativeCorrelation act(a(GO:lysosome)) View Subject | View Object

The profuse and selective accumulation of AVs in neurons in AD reflects a defect in the clearance of AVs by lysosomes rather than an abnormally elevated induction of autophagy PubMed:22908190

Appears in Networks:
Annotations
MeSH
Neurons

act(a(GO:lysosome)) increases a(GO:lysosome) View Subject | View Object

Indeed, primary lysosomal dysfunction in inherited congenital “lysosomal storage disorders” has long been recognized to cause severe neurodegenerative phenotypes characterized pathologically by accumulations of lysosomes and autophagic vacuoles [38] PubMed:18930136

Appears in Networks:

bp(GO:endocytosis) increases a(GO:lysosome) View Subject | View Object

This view was initially challenged by the observation that monoubiquitination operates as a key signal in endocytosis, a process important for numerous cell functions including lysosomal biogenesis [62] PubMed:18930136

Appears in Networks:

p(HGNC:CTSD) negativeCorrelation a(GO:lysosome) View Subject | View Object

The consequences of impaired lysosome function, for example, may be observed in cathepsin D knockout mice and Drosophila melanogaster cathepsin D mutants which show neurodegeneration and associated accumulation of autophagosomes and lysosomes [33–35]. PubMed:18930136

Appears in Networks:

path(MESH:"Neuronal Ceroid-Lipofuscinoses") negativeCorrelation act(a(GO:lysosome)) View Subject | View Object

For example, the neuronal ceroid lipofuscinoses (NCLs) are a heterogeneous group of inherited, neurodegenerative disorders with onset ranging from infancy to late adulthood that are caused by a variety of defects in lysosomal function. PubMed:18930136

Appears in Networks:

Out-Edges 16

a(GO:lysosome) increases deg(a(HBP:HBP00053)) View Subject | View Object

In agreement with our previous observations (Wang et al., 2009), we found that lysosomes contribute to degradation of WT tau (reflected as an increase in tau levels upon blockage of lysosomal proteolysis with inhibitors) PubMed:29024336

Appears in Networks:
Annotations
MeSH
Lysosomes
Confidence
High
MeSH
Brain

a(GO:lysosome) association p(HGNC:MAPT, var("p.Pro301Ser")) View Subject | View Object

Monomeric and aggregated tau-Dylight were also detected in LAMP1+late endosomes and lysosomes, consistent with endocytosed proteins first reaching early endosomes, before late endosomes and lysosomes PubMed:29590627

Appears in Networks:

a(GO:lysosome) increases tloc(p(HGNC:MAPT, var("p.Pro301Ser")), fromLoc(GO:"extracellular region"), toLoc(MESH:Neurons)) View Subject | View Object

Thus, monomeric and aggregated tau both efficiently enter neurons via the endosome/lysosome system, and they are actively trafficked within vesicles over long distances within neurons over several hours PubMed:29590627

Appears in Networks:

a(GO:lysosome) association a(HBP:"Tau aggregates") View Subject | View Object

Monomeric and aggregated tau-Dylight were also detected in LAMP1+late endosomes and lysosomes, consistent with endocytosed proteins first reaching early endosomes, before late endosomes and lysosomes PubMed:29590627

Appears in Networks:

a(GO:lysosome) increases tloc(a(HBP:"Tau aggregates"), fromLoc(GO:"extracellular region"), toLoc(MESH:Neurons)) View Subject | View Object

Thus, monomeric and aggregated tau both efficiently enter neurons via the endosome/lysosome system, and they are actively trafficked within vesicles over long distances within neurons over several hours PubMed:29590627

Appears in Networks:

a(GO:lysosome) decreases act(complex(GO:"NLRP3 inflammasome complex")) View Subject | View Object

Phagocytosis and subsequent lysosomal damage trigger by Aβ initiate the activation of the NLRP3 inflammasome in the microglia (Halle et al., 2008) PubMed:24561250

Appears in Networks:
Annotations
Cell Ontology (CL)
microglial cell
Confidence
High
NeuroMMSigDB
Amyloidogenic subgraph
NeuroMMSigDB
Endosomal lysosomal subgraph

a(GO:lysosome) increases deg(p(MESH:Proteins, pmod(Ub))) View Subject | View Object

It has recently become appreciated that ubiquitination of proteins by covalent modification tags them for elimination not only through the proteasome (the ubiquitin–proteasome system or UPS) but also through the lysosomal system. PubMed:22908190

Appears in Networks:

a(GO:lysosome) increases deg(p(HGNC:MAPT)) View Subject | View Object

It has been reported that tau is degraded by several major cellular degradation systems, including calpain, caspases, lysosomes, and proteasomes. PubMed:22908190

Appears in Networks:

a(GO:lysosome) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

A continuum of pathological changes of the lysosomal network unfolds in neurons as Alzheimer disease progresses, including dysregulation of endocytosis, increased lysosome biogenesis and, later, progressive failure of lysosomal clearance mechanisms (Fig. 6; Nixon et al. 2006). PubMed:22908190

Appears in Networks:

act(a(GO:lysosome)) negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

The profuse and selective accumulation of AVs in neurons in AD reflects a defect in the clearance of AVs by lysosomes rather than an abnormally elevated induction of autophagy PubMed:22908190

Appears in Networks:
Annotations
MeSH
Neurons

a(GO:lysosome) increases a(GO:organelle) View Subject | View Object

AVs and lysosomes constitute more than 95% of the organelles in dystrophic neuritic swellings in AD and AD mouse models, implying a cargo-specific defect in axonal transport, rather than a global one. PubMed:22908190

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(GO:lysosome) negativeCorrelation p(HGNC:CTSD) View Subject | View Object

The consequences of impaired lysosome function, for example, may be observed in cathepsin D knockout mice and Drosophila melanogaster cathepsin D mutants which show neurodegeneration and associated accumulation of autophagosomes and lysosomes [33–35]. PubMed:18930136

Appears in Networks:

act(a(GO:lysosome)) decreases path(HBP:Neurodegeneration) View Subject | View Object

Indeed, primary lysosomal dysfunction in inherited congenital “lysosomal storage disorders” has long been recognized to cause severe neurodegenerative phenotypes characterized pathologically by accumulations of lysosomes and autophagic vacuoles [38] PubMed:18930136

Appears in Networks:

act(a(GO:lysosome)) increases a(GO:autophagosome) View Subject | View Object

Indeed, primary lysosomal dysfunction in inherited congenital “lysosomal storage disorders” has long been recognized to cause severe neurodegenerative phenotypes characterized pathologically by accumulations of lysosomes and autophagic vacuoles [38] PubMed:18930136

Appears in Networks:

act(a(GO:lysosome)) increases a(GO:lysosome) View Subject | View Object

Indeed, primary lysosomal dysfunction in inherited congenital “lysosomal storage disorders” has long been recognized to cause severe neurodegenerative phenotypes characterized pathologically by accumulations of lysosomes and autophagic vacuoles [38] PubMed:18930136

Appears in Networks:

act(a(GO:lysosome)) negativeCorrelation path(MESH:"Neuronal Ceroid-Lipofuscinoses") View Subject | View Object

For example, the neuronal ceroid lipofuscinoses (NCLs) are a heterogeneous group of inherited, neurodegenerative disorders with onset ranging from infancy to late adulthood that are caused by a variety of defects in lysosomal function. PubMed:18930136

Appears in Networks:

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.