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bp(HP:Neurodegeneration)

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Entity

Name
Neurodegeneration
Namespace
HP
Namespace Version
2017-10-05
Namespace URL
https://arty.scai.fraunhofer.de/artifactory/bel/namespace/hp/hp-20171108.belns

Appears in Networks 9

Role of the nicotinic acetylcholine receptor in Alzheimer's disease pathology and treatment v1.0.1

The Biology of Proteostasis in Aging and Disease v1.0.0

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

Tau degradation: the ubiquitin-proteasome system versus the autophagy-lysosome system. v1.0.0

Tau protein aggregation is associated with cellular senescence in the brain v1.0.0

Tau oligomers-Cytotoxicity, propagation, and mitochondrial damage v1.0.0

Tau oligomers-Cytotoxicity, propagation, and mitochondrial damage from Shafiei et al., 2017

Tau oligomers and tau toxicity in neurodegenerative disease v1.0.0

Tau oligomers and tau toxicity in neurodegenerative disease by Ward et al., 2012

Molecular chaperones and proteostasis regulation during redox imbalance v1.0.0

Inhibition of tau aggregation in a novel Caenorhabditis elegans model of tauopathy mitigates proteotoxicity v1.0.0

In-Edges 25

a(CHEBI:methyllycaconitine) decreases bp(HP:Neurodegeneration) View Subject | View Object

Methyllycaconitine (MLA), an alpha7 nAChR antagonist, showed neuroprotective effect on mouse and rat primary cell culture (Martin et al., 2004) PubMed:25514383

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(MESH:"alpha7 Nicotinic Acetylcholine Receptor") decreases bp(HP:Neurodegeneration) View Subject | View Object

In this system enhancement of Akt phosphorylation and activation of ERK pathway was observed following alpha7 agonist treatment, suggesting that Abeta inhibits the neuroprotective effect of alpha7 nAChR activation (Zhi et al., 2014) PubMed:25514383

Appears in Networks:

act(a(MESH:"alpha7 Nicotinic Acetylcholine Receptor")) increases bp(HP:Neurodegeneration) View Subject | View Object

Methyllycaconitine (MLA), an alpha7 nAChR antagonist, showed neuroprotective effect on mouse and rat primary cell culture (Martin et al., 2004) PubMed:25514383

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

complex(a(CHEBI:"amyloid-beta"), a(MESH:"alpha7 Nicotinic Acetylcholine Receptor")) decreases bp(HP:Neurodegeneration) View Subject | View Object

The mechanism proposed is that the Aß-alpha7 nAChR interaction could activate neuroprotective downstream pathways (Parri et al., 2011), and that at the same time the interaction engages Abeta preventing its aggregation PubMed:25514383

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

act(p(FPLX:AKT)) decreases bp(HP:Neurodegeneration) View Subject | View Object

In a mouse model of AD, cotinine treatment decreased the plaque load and was able to activate the Akt pathway, that was shown to be neuroprotective (Echeverria et al., 2011) PubMed:25514383

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

p(MGI:Atg5) decreases bp(HP:Neurodegeneration) View Subject | View Object

Mice deficient for the autophagy-related genes Atg5 and Atg7 exhibit severe neurodegeneration (84, 85), and the expression of disease- associated proteins is reported to exert differential inhibitory effects on autophagic pathways. PubMed:25784053

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p(MGI:Atg7) decreases bp(HP:Neurodegeneration) View Subject | View Object

Mice deficient for the autophagy-related genes Atg5 and Atg7 exhibit severe neurodegeneration (84, 85), and the expression of disease- associated proteins is reported to exert differential inhibitory effects on autophagic pathways. PubMed:25784053

Appears in Networks:

a(CHEBI:"alpha,alpha-trehalose") decreases bp(HP:Neurodegeneration) View Subject | View Object

It also proved effective in cellu- lar models of PD, HD and AD 121,122 , as well as in mouse models of HD, AD and tauopathies, where it cleared aggregates, reduced neurodegeneration and ameliorated motor and cognitive performance 123–125 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons

a(CHEBI:Temsirolimus) decreases bp(HP:Neurodegeneration) View Subject | View Object

It also removed cellular aggregates of mutant Htt and improved motor performance in a mouse model of HD, reduced α-synuclein aggregation and afforded neuroprotection in a lesion-based model of PD and depleted mutant ataxin 3 in a mouse model of supraspinal cerebellar ataxia type 3 (REFS133,138,139) . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Parkinson Disease

a(CHEBI:nilotinib) decreases bp(HP:Neurodegeneration) View Subject | View Object

Inactivation of ABL1 with brain-penetrant nilotinib conferred neuroprotective autophagy in mouse models of PD 153 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Machado-Joseph Disease

a(PUBCHEM:16240819) decreases bp(HP:Neurodegeneration) View Subject | View Object

An unusual approach to augmenting autophagosome formation is represented by the brain- penetrant autophagy enhancer 99 (AUTEN-99), which blocks myotubularin-related protein 14 (MTMR14, also known as Jumpy), a phosphatase that inhibits the phos- phoinositide 3-kinase (PI3K)-mediated generation of the autophagosome membrane (FIG. 3) . AUTEN-99 aug- mented autophagic flux in isolated neurons, increased markers of autophagy in mouse brain and slowed neuro- degeneration in D. melanogaster models of PD and HD 181 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Machado-Joseph Disease

act(p(HGNC:RAB5A)) decreases bp(HP:Neurodegeneration) View Subject | View Object

Interestingly, genetic or pharmacological activation of RAB5 countered neurodegeneration in mouse C9ORF72 models of ALS and FTD 187 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Amyotrophic Lateral Sclerosis
MeSH
Frontotemporal Dementia

p(HBP:"UBB+1") increases bp(HP:Neurodegeneration) View Subject | View Object

UBB+ 1-capped polyUb chains are resistant to deubiquitination and inhibit proteasomal activity, which may mediate neurodegeneration through mitochondrial stress and p53 activation in neurites (Tan et al., 2007). PubMed:23528736

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bp(GO:"cellular senescence") increases bp(HP:Neurodegeneration) View Subject | View Object

Collectively, these findings indicate a strong association between the presence of NFTs and cellular senescence in the brain, which contributes to neurodegeneration PubMed:30126037

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

p(HGNC:CDKN2A) association bp(HP:Neurodegeneration) View Subject | View Object

Collectively, these findings led us to conclude that NFTs were directly linked to senescence-associated Cdkn2a upregulation, which in turn was a strong predictor of neurodegeneration and cognitive decline PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Parietal Lobe
MeSH
Supranuclear Palsy, Progressive

p(MGI:Mapt) increases bp(HP:Neurodegeneration) View Subject | View Object

However, genetically ablating endogenous mouse tau (microtubule associated protein tau, Mapt) reduces NFT pathology and neurodegeneration in tauNFT mice (tauNFT-Mapt0/0) (Wegmann et al., 2015) PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Alzheimer Disease

path(MESH:"Supranuclear Palsy, Progressive") increases bp(HP:Neurodegeneration) View Subject | View Object

PSP is an age-associated tauopathy that clinically manifests as parkinsonism with additional motor abnormalities and cognitive dysfunction (Orr et al., 2017), and is neuropathologically defined by accumulation of four-repeat (4R) tau, NFTs, gliosis and neurodegeneration (Flament et al., 1991) PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex
MeSH
Hippocampus
MeSH
Supranuclear Palsy, Progressive

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

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) PubMed:28420982

Appears in Networks:
Annotations
Confidence
High
MeSH
Cerebral Cortex

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

These studies demonstrate that tau oligomers may be the toxic entities responsible for neurodegeneration in tauopathies (Ward et al., 2012 PubMed:28420982

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Hippocampus

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

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) PubMed:28420982

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

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

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) PubMed:28420982

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Cerebral Cortex

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

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) PubMed:28420982

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

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

This indicates that tau oligomers represent the main toxic species responsible for neurodegeneration associated with AD PubMed:22817713

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Intracellular Space

bp(GO:"protein oxidation") association bp(HP:Neurodegeneration) View Subject | View Object

Proteome oxidation and instability has been associated with ageing and the progression of several age-related diseases, including cardiovascular disorders, neu- rodegeneration, and cancer [7,95,96]. PubMed:24563850

Appears in Networks:

a(HBP:cmp16) decreases bp(HP:Neurodegeneration) View Subject | View Object

Treatment with cmp16 diminished the progressive accumulation of neurite gaps in the motor neurons of the pro-aggregant animals compared with the DMSO-treated controls (from 3.2 + 1 gaps at day 5 of the DMSO-treated strains to 2.4 + 1 gaps of the cmp16-treated strains, P , 0.05) (Fig. 9B). Lower accumulation of structural damage in neurons can be interpreted as a sign of reduced neu- rodegeneration (22,58). PubMed:22611162

Appears in Networks:
Annotations
Cell Ontology (CL)
motor neuron
MeSH
Tauopathies

Out-Edges 3

bp(HP:Neurodegeneration) association p(HGNC:CDKN2A) View Subject | View Object

Collectively, these findings led us to conclude that NFTs were directly linked to senescence-associated Cdkn2a upregulation, which in turn was a strong predictor of neurodegeneration and cognitive decline PubMed:30126037

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Parietal Lobe
MeSH
Supranuclear Palsy, Progressive

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

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) PubMed:28420982

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Extracellular Fluid

bp(HP:Neurodegeneration) association bp(GO:"protein oxidation") View Subject | View Object

Proteome oxidation and instability has been associated with ageing and the progression of several age-related diseases, including cardiovascular disorders, neu- rodegeneration, and cancer [7,95,96]. PubMed:24563850

Appears in Networks:

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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.