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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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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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.