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bp(GO:"lysosomal protein catabolic process")

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Entity

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

Appears in Networks 4

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

Tau degradation: the ubiquitin-proteasome system versus the autophagy-lysosome system. 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 11

bp(GO:"protein ubiquitination") increases bp(GO:"lysosomal protein catabolic process") View Subject | View Object

In many of these cases, the modification leads to targeting of the tagged substrate for degradation in the lysosome/vacuole PubMed:14556719

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path(MESH:"Alzheimer Disease") decreases bp(GO:"lysosomal protein catabolic process") View Subject | View Object

The accumulated autophagic vacuoles in AD mainly reflect defected lysosomal clearance instead of induced autophagy. PubMed:23528736

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bp(GO:autophagy) positiveCorrelation bp(GO:"lysosomal protein catabolic process") View Subject | View Object

Even early autophagic activation may become impaired due to progressively diminishing lysosomal clearance of substrates. PubMed:29758300

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complex(p(HGNC:LAMP2), p(HGNC:SNCA, var("p.Ala30Pro"))) decreases bp(GO:"lysosomal protein catabolic process") View Subject | View Object

While wild-type α-synuclein protein efficiently clears via CMA, the pathogenic A53T and A30P variants remain bound to LAMP-2, blocking lysosomal degradation by preventing binding of other substrate complexes to the receptor [64]. PubMed:29758300

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complex(p(HGNC:LAMP2), p(HGNC:SNCA, var("p.Ala53Thr"))) decreases bp(GO:"lysosomal protein catabolic process") View Subject | View Object

While wild-type α-synuclein protein efficiently clears via CMA, the pathogenic A53T and A30P variants remain bound to LAMP-2, blocking lysosomal degradation by preventing binding of other substrate complexes to the receptor [64]. PubMed:29758300

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path(MESH:"Alzheimer Disease") negativeCorrelation bp(GO:"lysosomal protein catabolic process") View Subject | View Object

Such evidence of lysosomal proteolytic failure in AD brain further strengthens the concept that impaired macroautophagy in AD is a critical event PubMed:29758300

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Annotations
MeSH
Brain

bp(GO:autophagy) positiveCorrelation bp(GO:"lysosomal protein catabolic process") View Subject | View Object

Similar autophagy pathology is observed when lysosomal proteolysis is inhibited (Ivy et al. 1984; Koike et al. 2005; Yang et al. 2008). PubMed:22908190

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bp(GO:endocytosis) negativeCorrelation bp(GO:"lysosomal protein catabolic process") View Subject | View Object

Accelerated endocytosis also increases protein and lipid accumulation in endosomes and slows lysosomal degradation of endocytic cargoes (Cataldo et al. 2008), leading to lysosomal instability and neurodegeneration, as discussed below. PubMed:22908190

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Annotations
MeSH
Endosomes

p(HGNC:PSEN1, var("?")) decreases bp(GO:"lysosomal protein catabolic process") View Subject | View Object

That presenilin 1 mutations, which are a cause of early-onset familial AD, impede lysosome proteolysis and accelerate neuritic dystrophy also supports a primary role for failure of proteolytic clearance (Lee et al. 2010). PubMed:22908190

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act(p(HGNC:RAB5A)) negativeCorrelation bp(GO:"lysosomal protein catabolic process") View Subject | View Object

It is this abnormal rab5 activation that causes protein and lipid accumulation in endosomes, slowed lysosomal degradation of endocytic cargoes,endosome swelling (Cataldo et al. 2008), and disrupted retrograde transport of endosomes (S Kim and RA Nixon, unpubl.). PubMed:22908190

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path(MESH:"Alzheimer Disease") negativeCorrelation bp(GO:"lysosomal protein catabolic process") 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

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Out-Edges 19

bp(GO:"lysosomal protein catabolic process") decreases a(GO:autolysosome) View Subject | View Object

Other studies have also demonstrated the accumulation of autolysosomes in the AD brain and experimentally when lysosomal proteolysis is compromised via genetic knockdown of specific cathepsins or use of pharmacological inhibition of lysosomes [2,3,15] PubMed:29758300

Appears in Networks:
Annotations
MeSH
Brain

bp(GO:"lysosomal protein catabolic process") negativeCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Such evidence of lysosomal proteolytic failure in AD brain further strengthens the concept that impaired macroautophagy in AD is a critical event PubMed:29758300

Appears in Networks:
Annotations
MeSH
Brain

bp(GO:"lysosomal protein catabolic process") positiveCorrelation bp(GO:autophagy) View Subject | View Object

Even early autophagic activation may become impaired due to progressively diminishing lysosomal clearance of substrates. PubMed:29758300

Appears in Networks:

bp(GO:"lysosomal protein catabolic process") negativeCorrelation 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:

bp(GO:"lysosomal protein catabolic process") positiveCorrelation bp(GO:autophagy) View Subject | View Object

Similar autophagy pathology is observed when lysosomal proteolysis is inhibited (Ivy et al. 1984; Koike et al. 2005; Yang et al. 2008). PubMed:22908190

Appears in Networks:

bp(GO:"lysosomal protein catabolic process") negativeCorrelation act(p(HGNC:RAB5A)) View Subject | View Object

It is this abnormal rab5 activation that causes protein and lipid accumulation in endosomes, slowed lysosomal degradation of endocytic cargoes,endosome swelling (Cataldo et al. 2008), and disrupted retrograde transport of endosomes (S Kim and RA Nixon, unpubl.). PubMed:22908190

Appears in Networks:

bp(GO:"lysosomal protein catabolic process") increases bp(GO:"axonal transport") View Subject | View Object

Indeed, when lysosomal proteolysis is inhibited by blocking acidification or directly inhibiting cathepsins,axonal transport of autophagy-related compartments is selectively slowed and intermittently interrupted. PubMed:22908190

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bp(GO:"lysosomal protein catabolic process") negativeCorrelation bp(GO:endocytosis) View Subject | View Object

Accelerated endocytosis also increases protein and lipid accumulation in endosomes and slows lysosomal degradation of endocytic cargoes (Cataldo et al. 2008), leading to lysosomal instability and neurodegeneration, as discussed below. PubMed:22908190

Appears in Networks:
Annotations
MeSH
Endosomes

bp(GO:"lysosomal protein catabolic process") decreases path(HBP:Neurodegeneration) View Subject | View Object

Accelerated endocytosis also increases protein and lipid accumulation in endosomes and slows lysosomal degradation of endocytic cargoes (Cataldo et al. 2008), leading to lysosomal instability and neurodegeneration, as discussed below. PubMed:22908190

Appears in Networks:
Annotations
MeSH
Endosomes

bp(GO:"lysosomal protein catabolic process") decreases path(HBP:Neurodegeneration) View Subject | View Object

A close connection between lysosomal network dysfunction and mechanisms of neurodegeneration is well documented (McCray et al. 2008; Nixon et al. 2008; Bellettato et al. 2010; Cherra et al. 2010). PubMed:22908190

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bp(GO:"lysosomal protein catabolic process") decreases p(HGNC:MAP1LC3B) View Subject | View Object

In APP transgenic mouse models of AD, undigested autophagy substrates including LC3-II, p62, and ubiquitinated proteins accumulate in neuronal AVs, establishing that autophagic protein turnover in lysosomes is impeded (Yang et al. 2011). PubMed:22908190

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Annotations
MeSH
Alzheimer Disease

bp(GO:"lysosomal protein catabolic process") decreases p(HGNC:SQSTM1) View Subject | View Object

In APP transgenic mouse models of AD, undigested autophagy substrates including LC3-II, p62, and ubiquitinated proteins accumulate in neuronal AVs, establishing that autophagic protein turnover in lysosomes is impeded (Yang et al. 2011). PubMed:22908190

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

bp(GO:"lysosomal protein catabolic process") decreases p(MESH:Proteins, pmod(Ub)) View Subject | View Object

In APP transgenic mouse models of AD, undigested autophagy substrates including LC3-II, p62, and ubiquitinated proteins accumulate in neuronal AVs, establishing that autophagic protein turnover in lysosomes is impeded (Yang et al. 2011). PubMed:22908190

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

bp(GO:"lysosomal protein catabolic process") increases deg(a(MESH:"Amyloid beta-Peptides")) View Subject | View Object

AVs are also enriched in APP substrates and secretases and, during autophagy, Ab peptide is generated from APP (Yu et al. 2005), although it is subsequently degraded in lysosomes under normal circumstances (Heinrich et al. 1999; Bahr et al. 2002; Florez-McClure et al. 2007). PubMed:22908190

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bp(GO:"lysosomal protein catabolic process") increases deg(a(CHEBI:"amyloid-beta")) View Subject | View Object

Chronic low-level stimulation of autophagy through peripheral administration of rapamycin or other agents (Tian et al. 2011), or enhancing lysosomal proteolysis selectively (Sun et al. 2008; Yang et al. 2011), can markedly diminish Ab levels and amyloid load in APP transgenic mice, underscoring the importance of lysosomal clearance of Ab. PubMed:22908190

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bp(GO:"lysosomal protein catabolic process") increases deg(a(CHEBI:"amyloid-beta")) View Subject | View Object

Endocytic pathway up-regulation in AD stemming in part from pathological rab 5 activation generates higher levels of Ab (Mathews et al. 2002; Grbovic et al. 2003) that must be cleared in part by lysosomes. PubMed:22908190

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bp(GO:"lysosomal protein catabolic process") decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Stimulating lysosomal proteolytic efficiency in the TgCRND8 APP mouse model by deleting an endogenous inhibitor of lysosomal cysteine proteases (cystatin B) rescues lysosomal pathology, eliminates abnormal autolysosomal accumulation of autophagy substrates, including Ab, decreases Ab and amyloid deposition, and ameliorates learning and memory deficits (Yang et al. 2011) PubMed:22908190

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bp(GO:"lysosomal protein catabolic process") increases bp(GO:learning) View Subject | View Object

Stimulating lysosomal proteolytic efficiency in the TgCRND8 APP mouse model by deleting an endogenous inhibitor of lysosomal cysteine proteases (cystatin B) rescues lysosomal pathology, eliminates abnormal autolysosomal accumulation of autophagy substrates, including Ab, decreases Ab and amyloid deposition, and ameliorates learning and memory deficits (Yang et al. 2011) PubMed:22908190

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bp(GO:"lysosomal protein catabolic process") increases bp(GO:memory) View Subject | View Object

Stimulating lysosomal proteolytic efficiency in the TgCRND8 APP mouse model by deleting an endogenous inhibitor of lysosomal cysteine proteases (cystatin B) rescues lysosomal pathology, eliminates abnormal autolysosomal accumulation of autophagy substrates, including Ab, decreases Ab and amyloid deposition, and ameliorates learning and memory deficits (Yang et al. 2011) PubMed:22908190

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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.