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bp(MESH:Autophagy)

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Entity

Name
Autophagy
Namespace
MeSH
Namespace Version
20181007
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/01c9daa61012b37dd0a1bc962521ba51a15b38f1/external/mesh-names.belns

Appears in Networks 1

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

In-Edges 9

a(CHEBI:"methylene blue") increases bp(MESH:Autophagy) View Subject | View Object

Additionally, in a hippocampal slice preparation, induction of autophagy by treatment with methylene blue led to a decrease in phosphorylated tau and insoluble tau without an effect on total tau (95). PubMed:24027553

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MeSH
Hippocampus
Text Location
Review

a(CHEBI:sirolimus) increases bp(MESH:Autophagy) View Subject | View Object

Stimulating autophagy either through serum withdrawal or rapamycin treatment in SH-SY5Y cells overexpressing P301L tau that had been induced to aggregate led to substantial reduction in aggregates that was prevented by 3-MA (70). PubMed:24027553

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Review

a(MESH:"3-methyladenine") decreases bp(MESH:Autophagy) View Subject | View Object

Overexpressing only the repeat domain of tau containing an FTDP-17 mutation in neuroblastoma cells leads to tau aggregation as well as the appearance of smaller proteolytic fragments. Using the autophagy inhibitor 3-methyladenine (3-MA) to block the formation of autophagosomes led to an increase in both soluble and insoluble tau (94). PubMed:24027553

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MeSH
Frontotemporal Dementia
Text Location
Review

a(MESH:Trehalose) increases bp(MESH:Autophagy) View Subject | View Object

In a cell line expressing the repeat domain of tau containing the FTDP-17ΔK280 mutant, treatment with the disaccharide trehalose, an mTor-independent autophagy activator, significantly reduced aggregated tau as measured by Thioflavin-S staining, as well as total tau levels both soluble and insoluble as detected by western blotting (96). PubMed:24027553

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MeSH
Frontotemporal Dementia
Text Location
Review

a(MESH:Trehalose) increases 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

Appears in Networks:
Annotations
MeSH
Frontotemporal Dementia
Text Location
Review

a(MESH:Trehalose) increases bp(MESH:Autophagy) View Subject | View Object

Activating autophagy with trehalose in rat cortical neurons demonstrated certain phospho-epitopes (AT8, PHF1, and 12E8) were reduced more significantly than total tau – up to 80% compared to the 20% reduction in total tau (96). PubMed:24027553

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Review

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

Appears in Networks:
Annotations
MeSH
Frontotemporal Dementia
Text Location
Review

path(MESH:"Alzheimer Disease") positiveCorrelation bp(MESH:Autophagy) View Subject | View Object

This demonstrates that in the absence of mutant PS1, AD-associated impairment in autophagy occurs and thus is due to other factors. Treatment of ex vivo hippocampal slice cultures with lysosomal disruptors causes the formation of enlarged, dystrophic neurites filled with AVs and lysosomes, similar to what is seen in mouse AD models and human AD tissue (85, 86) PubMed:24027553

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path(MESH:"Alzheimer Disease") decreases bp(MESH:Autophagy) View Subject | View Object

However, as previously discussed, autophagy is likely impaired in AD. The tendency for certain phospho-epitopes to show preferential clearance by certain pathways may also relate to their propensity for aggregation. PubMed:24027553

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Review

Out-Edges 20

bp(MESH:Autophagy) decreases a(HBP:"Tau aggregates") View Subject | View Object

Stimulating autophagy either through serum withdrawal or rapamycin treatment in SH-SY5Y cells overexpressing P301L tau that had been induced to aggregate led to substantial reduction in aggregates that was prevented by 3-MA (70). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

bp(MESH:Autophagy) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

This demonstrates that in the absence of mutant PS1, AD-associated impairment in autophagy occurs and thus is due to other factors. Treatment of ex vivo hippocampal slice cultures with lysosomal disruptors causes the formation of enlarged, dystrophic neurites filled with AVs and lysosomes, similar to what is seen in mouse AD models and human AD tissue (85, 86) PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

bp(MESH:Autophagy) increases deg(p(HGNC:MAPT)) View Subject | View Object

Directly activating autophagy through a variety of mechanisms leads consistently to enhanced tau clearance – either pathological forms or total tau. In a hippocampal slice preparation methylene blue was used to induce autophagy, which resulted in a decrease in phosphorylated tau and insoluble tau, specifically (95). PubMed:24027553

Appears in Networks:
Annotations
MeSH
Hippocampus
Text Location
Review

bp(MESH:Autophagy) causesNoChange p(HGNC:MAPT) View Subject | View Object

Additionally, in a hippocampal slice preparation, induction of autophagy by treatment with methylene blue led to a decrease in phosphorylated tau and insoluble tau without an effect on total tau (95). PubMed:24027553

Appears in Networks:
Annotations
MeSH
Hippocampus
Text Location
Review

bp(MESH:Autophagy) increases deg(p(HGNC:MAPT, pmod(Ph))) View Subject | View Object

Directly activating autophagy through a variety of mechanisms leads consistently to enhanced tau clearance – either pathological forms or total tau. In a hippocampal slice preparation methylene blue was used to induce autophagy, which resulted in a decrease in phosphorylated tau and insoluble tau, specifically (95). PubMed:24027553

Appears in Networks:
Annotations
MeSH
Hippocampus
Text Location
Review

bp(MESH:Autophagy) increases deg(p(HGNC:MAPT, pmod(Ph))) View Subject | View Object

Additionally, in a hippocampal slice preparation, induction of autophagy by treatment with methylene blue led to a decrease in phosphorylated tau and insoluble tau without an effect on total tau (95). PubMed:24027553

Appears in Networks:
Annotations
MeSH
Hippocampus
Text Location
Review

bp(MESH:Autophagy) decreases p(HGNC:MAPT, var("p.P301L")) View Subject | View Object

Stimulating autophagy either through serum withdrawal or rapamycin treatment in SH-SY5Y cells overexpressing P301L tau that had been induced to aggregate led to substantial reduction in aggregates that was prevented by 3-MA (70). PubMed:24027553

Appears in Networks:
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Text Location
Review

bp(MESH:Autophagy) increases deg(a(HBP:"Tau aggregates")) View Subject | View Object

This is supported by evidence that full-length tau, which has a lower propensity for aggregating, is cleared by the proteasome while caspase- cleaved tau, which is more aggregate prone, goes through autophagy (72). Also, aggregated tau can be cleared by inducing autophagy (70, 96). PubMed:24027553

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Review

bp(MESH:Autophagy) increases deg(a(HBP:"Tau aggregates")) View Subject | View Object

Soluble, monomeric tau is an ideal proteasomal substrate. Indeed, it has been clearly demonstrated that tau can be degraded by the proteasome (65–67, 73). It thus can be suggested that under physiologic circumstances much of tau is degraded in this manner, with select modified forms being cleared by autophagy.However, within the context of the AD milieu, additional tau modifications and degradative impairments may cause the balance to shift away from proteasomal degradation toward autophagy. PubMed:24027553

Appears in Networks:
Annotations
MeSH
Alzheimer Disease
Text Location
Review

bp(MESH:Autophagy) increases deg(a(HBP:"Tau aggregates")) View Subject | View Object

For example, as discussed above, certain modified forms of tau, such as caspase-cleaved tau, have a stronger tendency to aggregate. As tau begins to assemble into oligomers, it may become increasingly undesirable as a proteasomal substrate. These low-order, soluble oligomers may be preferentially degraded by autophagy. PubMed:24027553

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Text Location
Review

bp(MESH:Autophagy) decreases p(MGI:Mapt, var("p.P301S")) 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

bp(MESH:Autophagy) decreases p(MGI:Mapt, pmod(Ph, Thr, 212), var("p.P301S")) 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

bp(MESH:Autophagy) decreases p(MGI:Mapt, pmod(Ph, Ser, 214), var("p.P301S")) 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

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

bp(MESH:Autophagy) increases deg(p(HBP:"Tau C3")) View Subject | View Object

This is supported by evidence that full-length tau, which has a lower propensity for aggregating, is cleared by the proteasome while caspase- cleaved tau, which is more aggregate prone, goes through autophagy (72). Also, aggregated tau can be cleared by inducing autophagy (70, 96). PubMed:24027553

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Review

bp(MESH:Autophagy) decreases p(HBP:"Tau C3") View Subject | View Object

Finally, caspase-3 cleaved tau has a shorter half-life than full-length tau and is preferentially degraded by autophagy (72). PubMed:24027553

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Review

bp(MESH:Autophagy) decreases a(HBP:"Tau epitope, AT8") View Subject | View Object

Activating autophagy with trehalose in rat cortical neurons demonstrated certain phospho-epitopes (AT8, PHF1, and 12E8) were reduced more significantly than total tau – up to 80% compared to the 20% reduction in total tau (96). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

bp(MESH:Autophagy) decreases a(HBP:"Tau epitope, PHF1") View Subject | View Object

Activating autophagy with trehalose in rat cortical neurons demonstrated certain phospho-epitopes (AT8, PHF1, and 12E8) were reduced more significantly than total tau – up to 80% compared to the 20% reduction in total tau (96). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

bp(MESH:Autophagy) decreases a(HBP:"Tau epitope, 12E8") View Subject | View Object

Activating autophagy with trehalose in rat cortical neurons demonstrated certain phospho-epitopes (AT8, PHF1, and 12E8) were reduced more significantly than total tau – up to 80% compared to the 20% reduction in total tau (96). PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

bp(MESH:Autophagy) increases deg(a(HBP:"Tau oligomers")) View Subject | View Object

For example, as discussed above, certain modified forms of tau, such as caspase-cleaved tau, have a stronger tendency to aggregate. As tau begins to assemble into oligomers, it may become increasingly undesirable as a proteasomal substrate. These low-order, soluble oligomers may be preferentially degraded by autophagy. PubMed:24027553

Appears in Networks:
Annotations
Text Location
Review

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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.