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PubMed: 28420982

Title
Tau Oligomers: Cytotoxicity, Propagation, and Mitochondrial Damage.
Journal
Frontiers in aging neuroscience
Volume
9
Issue
None
Pages
83
Date
2017-01-01
Authors
Castillo-Carranza DL | Guerrero-Muñoz MJ | Shafiei SS

Evidence 995ebefd9c
JSON

In fact, tau oligomers might disrupt microtubule stability and trafficking, thus affecting organelle distribution

a(HBP:"Tau oligomers") decreases act(a(GO:microtubule)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Neurons
MeSH
Alzheimer Disease

Evidence 17bd8cc8e3
JSON

Evidence shows that tau aggregates colocalize with dextran and HeLa cells, hinting that internalized aggregates are transported in endosomal vesicles and passed through the endosomal pathway to lysosomes (Wu et al., 2013)

a(CHEBI:dextran) association a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Exosomes
MeSH
Alzheimer Disease

a(HBP:"Tau aggregates") association a(CHEBI:dextran) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Exosomes
MeSH
Alzheimer Disease

bp(GO:endocytosis) increases tloc(a(HBP:"Tau aggregates"), fromLoc(GO:endosome), toLoc(GO:lysosome)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Exosomes
MeSH
Alzheimer Disease

Evidence 152bbf5cb1
JSON

Compared to non-demented controls, AD brains exhibit up to 50% of neuronal loss in the cortex, exceeding the number of NFTs (Gómez-Isla et al., 1997)

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

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex

bp(GO:"neuron death") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex

path(MESH:"Alzheimer Disease") positiveCorrelation bp(GO:"neuron death") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex

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

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex

Evidence 582b5f61f2
JSON

Recently, more evidence implies that the secretion of tau occurs through unconventional cellular pathways via vesicles known as exosomes (Saman et al., 2012) and ectosomes (Dujardin et al., 2014a)

a(GO:microvesicle) association sec(p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Neocortex

a(MESH:Exosomes) association sec(p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Neocortex

sec(p(HGNC:MAPT)) association a(MESH:Exosomes) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Neocortex

sec(p(HGNC:MAPT)) association a(GO:microvesicle) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Neocortex

Evidence e934bd3618
JSON

Significantly, evidence suggests that tau secretion is partly mediated by ectosomal vesicles and that pathological tau accumulation in cells leads to a deviation toward tau secretion by exosomal vesicles (Dujardin et al., 2014a)

a(GO:microvesicle) regulates sec(p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Microglia
MeSH
Alzheimer Disease

a(HBP:"Tau aggregates") association sec(p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Exosomes
MeSH
Alzheimer Disease

sec(p(HGNC:MAPT)) association a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Exosomes
MeSH
Alzheimer Disease

Evidence a62d8eae49
JSON

These share a common histopathological hallmark known as neurofibrillary tangles (NFTs) that consist of an accumulation of fibrillar tau deposits initially produced from tau protein aggregation (Ballatore et al., 2007)

a(HBP:"Tau aggregates") increases a(GO:"neurofibrillary tangle") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

Evidence e2365a0a25
JSON

Additionally, studies have discovered that aggregated tau inhibits fast axonal transport in the anterograde direction at all physiological tau levels, whereas tau monomers have had no effect in either direction (LaPointe et al., 2009; Morfini et al., 2009)

a(HBP:"Tau aggregates") decreases bp(GO:"anterograde axonal protein transport") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex

Evidence c0a769a16b
JSON

A recent study showed that neuronal networks facilitate cell-to-cell transfer of tau via synapses; using a microfluidic device they demonstrated that decreasing synaptic connections weakens tau transfer and the subsequent aggregation on the acceptor cell (Calafate et al., 2015)

a(HBP:"Tau aggregates") association bp(MESH:"Neuronal Plasticity") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Low
MeSH
Entorhinal Cortex

bp(MESH:"Neuronal Plasticity") increases tloc(p(HGNC:MAPT), fromLoc(GO:cell), toLoc(GO:cell)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Low
MeSH
Entorhinal Cortex

bp(MESH:"Neuronal Plasticity") association a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Low
MeSH
Entorhinal Cortex

Evidence de2849337d
JSON

Hence, tau APFs may play a significant role in tauopathies by linking pore formation to cell death

a(HBP:"Tau annular protofibrils") association path(MESH:Tauopathies) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Neurons
MeSH
Alzheimer Disease

path(MESH:Tauopathies) association a(HBP:"Tau annular protofibrils") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Neurons
MeSH
Alzheimer Disease

Evidence e42e5006d8
JSON

As these granular tau oligomers fuse together, they form tau fibrils, which ultimately form NFTs (Takashima, 2013)

a(HBP:"Tau fibrils") increases a(GO:"neurofibrillary tangle") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex

a(HBP:"granular tau oligomers") increases a(HBP:"Tau fibrils") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex

Evidence 8ce4bbccc5
JSON

While evidence indicates that these deposits are not toxic, many studies suggest that the tau oligomer, an intermediate entity, is likely responsible for disease onset

a(HBP:"Tau oligomers") increases path(MESH:Disease) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Low
MeSH
Cerebral Cortex

Evidence 69522f07fd
JSON

These tau oligomers potentiate neuronal damage, leading to neurodegeneration and traumatic brain injury (Hawkins et al., 2013; Gerson et al., 2014a, 2016; Sengupta et al., 2015). Moreover, they have been implicated in synaptic loss as shown in studies of wild-type human tau transgenic mice (Spires et al., 2006; Berger et al., 2007; Clavaguera et al., 2013)

a(HBP:"Tau oligomers") increases bp(HP:Neurodegeneration) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex

a(HBP:"Tau oligomers") increases path(MESH:"Brain Injuries, Traumatic") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex

a(HBP:"Tau oligomers") decreases a(GO:synapse) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex

Evidence 45e5f3e214
JSON

These studies demonstrate that tau oligomers may be the toxic entities responsible for neurodegeneration in tauopathies (Ward et al., 2012

a(HBP:"Tau oligomers") increases bp(HP:Neurodegeneration) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Hippocampus

a(HBP:"Tau oligomers") increases path(MESH:Tauopathies) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Hippocampus

Evidence 4fa090eacf
JSON

When the oligomer lengthens, it adapts a beta-sheet structure and transforms into a detergent-insoluble aggregate with granular appearance under Atomic Force Microscopy (AFM)

a(HBP:"Tau oligomers") increases a(HBP:"granular tau oligomers") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex

Evidence 2f3e7efb37
JSON

The onset of clinical symptoms in AD and PSP brains correlate with elevated levels of tau oligomer (Maeda et al., 2006, 2007; Patterson et al., 2011; Lasagna-Reeves et al., 2012b; Gerson et al., 2014a)

a(HBP:"Tau oligomers") positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex

a(HBP:"Tau oligomers") positiveCorrelation path(MESH:"Supranuclear Palsy, Progressive") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex

path(MESH:"Alzheimer Disease") positiveCorrelation a(HBP:"Tau oligomers") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex

path(MESH:"Supranuclear Palsy, Progressive") positiveCorrelation a(HBP:"Tau oligomers") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex

Evidence b6aff121b8
JSON

When tau oligomers, rather than tau monomers or fibrils, are injected into the brain of wild-type mice, cognitive, synaptic, and mitochondrial abnormalities follow (Lasagna- Reeves et al., 2011; Castillo-Carranza et al., 2014b)

a(HBP:"Tau oligomers") decreases bp(GO:cognition) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex

a(HBP:"Tau oligomers") decreases bp(GO:"mitochondrion organization") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex

a(HBP:"Tau oligomers") decreases bp(GO:"maintenance of synapse structure") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex

Evidence 2300e12bfc
JSON

This indicates that tauopathies progress via a prion-like mechanism dependent upon tau oligomers (Gerson and Kayed, 2013; Castillo-Carranza et al., 2014b)

a(HBP:"Tau oligomers") increases path(MESH:Tauopathies) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex

Evidence c15475983a
JSON

With this concept, tau may be able to translocate between neurons and augment toxic tau components; in fact, evidence suggests probability of tau oligomer propagation between synaptically connected neurons (Gendreau and Hall, 2013; Pooler et al., 2013b)

a(HBP:"Tau oligomers") increases tloc(p(HGNC:MAPT), fromLoc(GO:"neuron part"), toLoc(GO:"neuron part")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Low
MeSH
Cerebral Cortex

Evidence f445a1d294
JSON

Further, mice injected with tau oligomers in the proximity of the hippocampus experienced immediate memory impairment (Lasagna-Reeves et al., 2011)

a(HBP:"Tau oligomers") decreases bp(GO:memory) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Hippocampus

Evidence d51189e6ed
JSON

The study discovered that APFs form after tau oligomer formation and bypass higher NFT aggregate formation

a(HBP:"Tau oligomers") increases a(HBP:"Tau annular protofibrils") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Neurons
MeSH
Alzheimer Disease

Evidence ffdbcbb3ed
JSON

Oligomeric tau intermediates decrease cell viability (Flach et al., 2012)

a(HBP:"Tau oligomers") decreases bp(MESH:"Cell Survival") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Neurons
MeSH
Alzheimer Disease

Evidence a959d632d6
JSON

Recently, data has shown that injected tau oligomers colocalize with the mitochondrial marker porin, suggesting a pathological relationship

a(HBP:"Tau oligomers") association p(HGNC:PRNP) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Neurons
MeSH
Alzheimer Disease

p(HGNC:PRNP) association a(HBP:"Tau oligomers") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Neurons
MeSH
Alzheimer Disease

Evidence e226249543
JSON

Also, data shows low levels of complex I in brain hemispheres injected with tau oligomers when compared to brains injected with monomers or fibrils

a(HBP:"Tau oligomers") decreases a(MESH:"Electron Transport Complex I") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Neurons
MeSH
Alzheimer Disease

Evidence 9e2fc9d91f
JSON

These results imply that tau oligomers initially affect complex I activity and may directly or indirectly disturb the later stage of complex V ATP synthesis (Lasagna-Reeves et al., 2011)

a(HBP:"Tau oligomers") decreases act(a(MESH:"Electron Transport Complex I")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Neurons
MeSH
Alzheimer Disease

a(HBP:"Tau oligomers") decreases bp(GO:"ATP synthesis coupled proton transport") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Neurons
MeSH
Alzheimer Disease

Evidence 9a1e592e94
JSON

Hemispheres injected with tau oligomers were found to have increased levels of caspase-9 activation (Lasagna-Reeves et al., 2011)

a(HBP:"Tau oligomers") increases act(p(HGNC:CASP9)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Neurons
MeSH
Alzheimer Disease

Evidence 68de1cd5e2
JSON

Suggestively, as tau oligomers concentrate at the mitochondrial membrane, cytochrome C is released, leading to caspase-9 activation via a complex with apoptotic-peptidase activating- factor-1 (Apaf-1; Li et al., 1997)

a(HBP:"Tau oligomers") increases sec(p(HGNC:CYCS)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Mitochondrial Membranes
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

complex(p(HGNC:APAF1), p(HGNC:CYCS)) increases act(p(HGNC:CASP9)) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Mitochondrial Membranes
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

Evidence e2a353e6d0
JSON

HSPGs are ubiquitously expressed in many cell types including neurons, and have been previously associated with dense core plaques, cerebrovascular amyloid, and NFT formation (van Horssen et al., 2001)

a(HBP:"dense core plaques") association a(MESH:"Heparan Sulfate Proteoglycans") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Exosomes
MeSH
Alzheimer Disease

a(MESH:"Heparan Sulfate Proteoglycans") association bp(GO:"neurofibrillary tangle assembly") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Exosomes
MeSH
Alzheimer Disease

a(MESH:"Heparan Sulfate Proteoglycans") association a(HBP:"dense core plaques") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Exosomes
MeSH
Alzheimer Disease

a(MESH:"Heparan Sulfate Proteoglycans") association path(MESH:"Cerebral Amyloid Angiopathy, Familial") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Exosomes
MeSH
Alzheimer Disease

bp(GO:"neurofibrillary tangle assembly") association a(MESH:"Heparan Sulfate Proteoglycans") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Exosomes
MeSH
Alzheimer Disease

path(MESH:"Cerebral Amyloid Angiopathy, Familial") association a(MESH:"Heparan Sulfate Proteoglycans") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Exosomes
MeSH
Alzheimer Disease

Evidence 96f9d19256
JSON

Consistently, HSPGs have been implicated in amyloid as well as tau fibril formation in vitro, presumably facilitated by anionic moieties

a(MESH:"Heparan Sulfate Proteoglycans") increases a(HBP:"Tau fibrils") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Exosomes
MeSH
Alzheimer Disease

a(MESH:"Heparan Sulfate Proteoglycans") increases a(HBP:"amyloid-beta fibrils") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Exosomes
MeSH
Alzheimer Disease

Evidence b384ca363b
JSON

However, regardless of the multiple “sizes” of tau aggregates that interact with the cell surface via HSPGs, it is likely that an assembly of at least three tau molecules is required to initiate endocytosis via HSPGs (Mirbaha et al., 2015)

a(MESH:"Heparan Sulfate Proteoglycans") increases complex(a(GO:"cell surface"), a(HBP:"Tau aggregates")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Exosomes
MeSH
Alzheimer Disease

Evidence 6de26b34e3
JSON

In other words, the HSPGs serve as a receptor for the cellular uptake of tau, a critical step similar to prion-like propagation

a(MESH:"Heparan Sulfate Proteoglycans") increases tloc(p(HGNC:MAPT), fromLoc(GO:"extracellular space"), toLoc(GO:"intracellular part")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Exosomes
MeSH
Alzheimer Disease

Evidence 8b6336d5ef
JSON

AD brain samples contain exosomal proteins within amyloid plaques hinting that exosomes play part in disease pathology (Rajendran et al., 2006)

a(MESH:Exosomes) association path(MESH:"Plaque, Amyloid") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Neocortex
MeSH
Alzheimer Disease

path(MESH:"Plaque, Amyloid") association a(MESH:Exosomes) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Neocortex
MeSH
Alzheimer Disease

Evidence 6c1f48a044
JSON

In support, tau associated with exosomes and phosphorylated at Thr-181 (AT270+ tau) has been identified in human CSF samples of AD patients

a(MESH:Exosomes) association p(HGNC:MAPT, pmod(Ph, Thr, 181)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebrospinal Fluid
MeSH
Alzheimer Disease

p(HGNC:MAPT, pmod(Ph, Thr, 181)) association a(MESH:Exosomes) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebrospinal Fluid
MeSH
Alzheimer Disease

Evidence e891659347
JSON

This hints that tau plays a role in monitoring intracellular signaling pathways (Pooler and Hanger, 2010)

bp(GO:"intracellular signal transduction") association p(HGNC:MAPT) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Hippocampus

p(HGNC:MAPT) association bp(GO:"intracellular signal transduction") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Hippocampus

Evidence 803da88f7d
JSON

In aging, a protein involved in mitochondrial fission, dynamin-related protein 1 (DRP1), can bind tau abnormally, inducing neurodegeneration via mitochondrial dysfunction (Figure 2; DuBoff et al., 2012)

bp(GO:"mitochondrion organization") decreases bp(HP:Neurodegeneration) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

complex(p(HGNC:DNM1L), p(HGNC:MAPT)) increases bp(HP:Neurodegeneration) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
Medium
MeSH
Neurons
MeSH
Alzheimer Disease

Evidence e90add2e1f
JSON

In AD, tau pathology and neuronal cell loss coincide in the same brain regions, and as brain dysfunction progresses, NFTs are found in greater anatomical distributions (Ihara, 2001)

bp(GO:"neuron death") association path(MESH:Tauopathies) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

path(MESH:Tauopathies) association bp(GO:"neuron death") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

Evidence 582b03005c
JSON

While evidence has linked FTD with parkinsonism in patients to tau mutations on chromosome 17 (FTDP-17), implying that tau dysfunction alone can cause neurodegeneration (Reed et al., 2001), studies in animal models have shown that overexpression of tau can lead to cell death (Lee et al., 2001; Tanemura et al., 2001, 2002; Tatebayashi et al., 2002) and exhibit behavioral abnormalities and synaptic dysfunction without the presence of NFTs (Wittmann et al., 2001; Andorfer et al., 2003; Santacruz et al., 2005; Spires et al., 2006; Berger et al., 2007; Yoshiyama et al., 2007; Cowan et al., 2010)

bp(GO:behavior) association p(HGNC:MAPT) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex

p(HGNC:MAPT) increases bp(HP:Neurodegeneration) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex

p(HGNC:MAPT) increases bp(GO:"cell death") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex

p(HGNC:MAPT) association bp(GO:behavior) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex

p(HGNC:MAPT) decreases bp(GO:"synaptic signaling") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex

Evidence c7c77b3fea
JSON

Recently, tau was discovered in the interstitial fluid of awake, wild-type mice, suggesting its release by neurons in the absence of neurodegeneration (Yamada et al., 2011)

bp(HP:Neurodegeneration) decreases sec(p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Extracellular Fluid

Evidence a9aa1beb0b
JSON

Further, transgenic mouse lines expressing human tau aggregates in the entorhinal cortex have shown that tau is mislocalized from axons to cell bodies and dendrites as the mice age (Pooler et al., 2013b)

bp(MESH:Aging) association tloc(p(HGNC:MAPT), fromLoc(GO:axon), toLoc(GO:"cell body")) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Entorhinal Cortex

bp(MESH:Aging) association tloc(p(HGNC:MAPT), fromLoc(GO:axon), toLoc(GO:dendrite)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Entorhinal Cortex

tloc(p(HGNC:MAPT), fromLoc(GO:axon), toLoc(GO:"cell body")) association bp(MESH:Aging) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Entorhinal Cortex

tloc(p(HGNC:MAPT), fromLoc(GO:axon), toLoc(GO:dendrite)) association bp(MESH:Aging) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Entorhinal Cortex

Evidence 2e95f94e94
JSON

In the latter theory, during the secretion, vesicles and the cell membrane can be fused and uncoated tau protein can be released to the extracellular space (Clavaguera et al., 2009; Iba et al., 2013)

complex(a(GO:vesicle), a(MESH:"Cell Membrane")) increases sec(p(HGNC:MAPT)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Exosomes
MeSH
Alzheimer Disease

Evidence d94cf2af76
JSON

Previous studies suggest that uptake of aggregated tau from the extracellular space depends on interaction with heparan sulfate proteoglycans (HSPGs; Holmes and Diamond, 2014)

complex(a(HBP:"Tau aggregates"), a(MESH:"Heparan Sulfate Proteoglycans")) increases tloc(a(HBP:"Tau aggregates"), fromLoc(GO:"extracellular space"), toLoc(GO:"intracellular part")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Exosomes
MeSH
Alzheimer Disease

Evidence ee788b5883
JSON

Basically, pathogenic tau aggregates use HSPGs to bind the cell surface of a neuron. This actively stimulates macropinocytosis, leading to propagation of aggregates between cells in culture and aggregate uptake in vivo (Holmes et al., 2013)

complex(a(HBP:"Tau aggregates"), a(MESH:"Heparan Sulfate Proteoglycans")) increases a(HBP:"Tau aggregates") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Neurons
MeSH
Alzheimer Disease

complex(a(HBP:"Tau aggregates"), a(MESH:"Heparan Sulfate Proteoglycans")) increases complex(a(GO:"cell surface"), a(HBP:"Tau aggregates")) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Neurons
MeSH
Alzheimer Disease

complex(a(HBP:"Tau aggregates"), a(MESH:"Heparan Sulfate Proteoglycans")) increases bp(GO:macropinocytosis) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Neurons
MeSH
Alzheimer Disease

Evidence b2749a4357
JSON

While functional tau is an unfolded monomeric protein that stabilizes microtubules, regulates neurite growth, and monitors axonal transport of organelles (Medina and Avila, 2014), dysfunctional tau acquires a new toxic function

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

Appears in Networks:
Annotations
Confidence
High

p(HGNC:MAPT) regulates bp(GO:"generation of neurons") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

p(HGNC:MAPT) regulates bp(GO:"axonal transport") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High

Evidence e2a7a7c5a2
JSON

In AD, the quantity of tau identified in the CSF increases with disease progression (Hampel et al., 2010). However, the mechanism of tau propagation from the brain to the CSF remains elusive

p(HGNC:MAPT) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebrospinal Fluid

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebrospinal Fluid

Evidence bc03fe81dd
JSON

More recently, patients affected with FTD and AD, were found to have high levels of total tau and phosphorylated tau (p-T181 and p-S396; Saman et al., 2012)

p(HGNC:MAPT) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebrospinal Fluid
MeSH
Alzheimer Disease

p(HGNC:MAPT) positiveCorrelation path(MESH:"Frontotemporal Dementia") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebrospinal Fluid
MeSH
Alzheimer Disease

p(HGNC:MAPT, pmod(Ph, Ser, 396)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebrospinal Fluid
MeSH
Alzheimer Disease

p(HGNC:MAPT, pmod(Ph, Ser, 396)) positiveCorrelation path(MESH:"Frontotemporal Dementia") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebrospinal Fluid
MeSH
Alzheimer Disease

p(HGNC:MAPT, pmod(Ph, Thr, 181)) positiveCorrelation path(MESH:"Alzheimer Disease") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebrospinal Fluid
MeSH
Alzheimer Disease

p(HGNC:MAPT, pmod(Ph, Thr, 181)) positiveCorrelation path(MESH:"Frontotemporal Dementia") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebrospinal Fluid
MeSH
Alzheimer Disease

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebrospinal Fluid
MeSH
Alzheimer Disease

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebrospinal Fluid
MeSH
Alzheimer Disease

path(MESH:"Alzheimer Disease") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Thr, 181)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebrospinal Fluid
MeSH
Alzheimer Disease

path(MESH:"Frontotemporal Dementia") positiveCorrelation p(HGNC:MAPT) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebrospinal Fluid
MeSH
Alzheimer Disease

path(MESH:"Frontotemporal Dementia") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Ser, 396)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebrospinal Fluid
MeSH
Alzheimer Disease

path(MESH:"Frontotemporal Dementia") positiveCorrelation p(HGNC:MAPT, pmod(Ph, Thr, 181)) View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebrospinal Fluid
MeSH
Alzheimer Disease

Evidence c16d1a8017
JSON

Tau may be endocytosed, promoting an increase in intracellular calcium that results in neuronal death

p(HGNC:MAPT) increases a(CHEBI:"calcium(2+)") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Intracellular Space
Confidence
Medium
MeSH
Exosomes
MeSH
Alzheimer Disease

p(HGNC:MAPT) increases bp(GO:"neuron death") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Exosomes
MeSH
Alzheimer Disease

Evidence a77c09bae6
JSON

In other words, it is sensible to theorize that tauopathies progress via interaction of extracellular tau with M1 and M3 receptors on neurons leading to cytotoxic effects (Gómez-Ramos et al., 2009)

complex(p(HGNC:CHRM1), p(HGNC:MAPT)) increases path(MESH:Tauopathies) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Exosomes
MeSH
Alzheimer Disease

complex(p(HGNC:CHRM3), p(HGNC:MAPT)) increases path(MESH:Tauopathies) View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
High
MeSH
Exosomes
MeSH
Alzheimer Disease

Evidence a2fcf7d5bb
JSON

Another study showed that expression of tau (truncated at Asp-421 to mimic caspase cleavage) caused mitochondrial dysfunction (Quintanilla et al., 2009)

p(HGNC:MAPT, frag("1_421")) decreases bp(GO:"mitochondrion organization") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
Low
MeSH
Neurons
MeSH
Alzheimer Disease

p(HGNC:MAPT, frag("421_?")) decreases bp(GO:"mitochondrion organization") View Subject | View Object

Appears in Networks:
Annotations
MeSH
Extracellular Space
Confidence
Low
MeSH
Neurons
MeSH
Alzheimer Disease

Evidence c147601396
JSON

Hyper-phosphorylated tau assembles into small aggregates known as tau oligomers in route of NFT formation

p(HGNC:MAPT, pmod(Ph)) increases a(HBP:"Tau oligomers") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex

p(HGNC:MAPT, pmod(Ph)) increases a(GO:"neurofibrillary tangle") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex

Evidence 288d8524a0
JSON

As hyperphosphorylated tau dislodges from microtubules, its affinity for other tau monomers leads individual tau to bind each other, forming oligomeric tau, a detergent-soluble aggregate

p(HGNC:MAPT, pmod(Ph)) increases a(HBP:"Tau oligomers") View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex

Evidence d00c63f02d
JSON

In AD, tau pathology has been found to spread from the transentorhinal cortex to the neocortex in a sequential pathway

path(MESH:"Alzheimer Disease") increases p(HGNC:MAPT) View Subject | View Object

Appears in Networks:
Annotations
Confidence
High
MeSH
Neocortex

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.