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Appears in Networks 9

In-Edges 24

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.