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a(HBP:HBP00016)

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Entity

Name
HBP00016
Namespace
HBP
Namespace Version
20181029
Namespace URL
https://raw.githubusercontent.com/pharmacome/terminology/785431732a26d6809b4162d98b95687d16404e63/export/hbp.belns

Appears in Networks 3

Alpha-synuclein oligomers: a new hope v1.0.0

Structural and functional properties of prefibrillar α-synuclein oligomers v1.0.0

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

In-Edges 17

a(CHEBI:"(-)-epigallocatechin 3-gallate") decreases a(HBP:HBP00016) View Subject | View Object

Epigallocatechin-3-gallate (EGCG), a small molecule that been shown to inhibit the aggregation of several amyloidogenic proteins such as a-syn, amyloid-beta and huntingtin [9, 37, 38, 105] binds to unfolded native amyloid-beta and a-syn and promotes the formation of nontoxic oligomers that do not convert into amyloid fibrils [37]. PubMed:28803412

Appears in Networks:
Annotations
Confidence
High
MeSH
Brain
MeSH
Cerebrospinal Fluid
MeSH
Serum

a(CHEBI:curcumin) decreases a(HBP:HBP00016) View Subject | View Object

In vitro studies have shown that curcumin inhibited the formation of fibrils and disaggregated amyloid-beta and a-syn [112, 114, 155]. PubMed:28803412

Appears in Networks:
Annotations
Confidence
High
MeSH
Brain
MeSH
Cerebrospinal Fluid
MeSH
Serum

a(HBP:HBP00094) decreases a(HBP:HBP00016) View Subject | View Object

Prabhudesai et al. showed that this molecule is able to inhibit the aggregation of a-syn in vitro and in a zebrafish model expressing human wild-type a-syn in neurons where CLR01 reduced apoptosis and improved embryo survival [127]. PubMed:28803412

Appears in Networks:
Annotations
Confidence
High
MeSH
Brain
MeSH
Cerebrospinal Fluid
MeSH
Serum

a(HBP:HBP00092) increases a(HBP:HBP00016) View Subject | View Object

The high proportion of cells with overlapping ChFP and ATTO-488 puncta (89 ± 7% upon cell exposure to 0.06 nM ATTO-488-labeled α -syn fibrils, Fig. 6f) indicates that α -syn fibrils seed with high efficiency the aggregation of soluble cytoplasmic ChFP-α -syn. PubMed:27075649

Appears in Networks:
Annotations
MeSH
Intracellular Space
Cell Ontology (CL)
neuron
Confidence
Low
MeSH
Lewy Bodies

a(HBP:HBP00095) increases a(HBP:HBP00016) View Subject | View Object

Prefibrillar oligomeric α -syn has been proposed to contribute to neurodegeneration by perturbing cellular ion homeostasis20, by seeding the assembly of soluble α -syn into higher molecular weight aggregates21, and/or by imbalancing cellular proteostasis22,23. PubMed:27075649

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Lewy Bodies

path(MESH:"Lewy Body Disease") positiveCorrelation a(HBP:HBP00016) View Subject | View Object

Parkinson’s disease (PD), Multiple System Atrophy (MSA) and Dementia with Lewy Bodies (DLB) are devastating synucleinopathies. The deposition of filamentous insoluble protein inclusions termed Lewy bodies and Lewy neurites whose main constituent is aggregated α -synuclein (α -syn) characterizes synucleinopathies. PubMed:27075649

Appears in Networks:
Annotations
Confidence
High
MeSH
Lewy Bodies

path(MESH:"Multiple System Atrophy") positiveCorrelation a(HBP:HBP00016) View Subject | View Object

Parkinson’s disease (PD), Multiple System Atrophy (MSA) and Dementia with Lewy Bodies (DLB) are devastating synucleinopathies. The deposition of filamentous insoluble protein inclusions termed Lewy bodies and Lewy neurites whose main constituent is aggregated α -synuclein (α -syn) characterizes synucleinopathies. PubMed:27075649

Appears in Networks:
Annotations
Confidence
High
MeSH
Lewy Bodies

path(MESH:"Parkinson Disease") positiveCorrelation a(HBP:HBP00016) View Subject | View Object

Parkinson’s disease (PD), Multiple System Atrophy (MSA) and Dementia with Lewy Bodies (DLB) are devastating synucleinopathies. The deposition of filamentous insoluble protein inclusions termed Lewy bodies and Lewy neurites whose main constituent is aggregated α -synuclein (α -syn) characterizes synucleinopathies. PubMed:27075649

Appears in Networks:
Annotations
Confidence
High
MeSH
Lewy Bodies

a(CHEBI:"alpha,alpha-trehalose") decreases a(HBP:HBP00016) 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:Isorhynchophylline) decreases a(HBP:HBP00016) View Subject | View Object

In addition, the plant-derived alkaloid isorhynchophylline upregulated beclin 1 independently of mTORC1 and promoted autophagic clearance of α-synuclein, although its precise mechanism of action remains to be clarified 175 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Machado-Joseph Disease

a(CHEBI:Temsirolimus) decreases a(HBP:HBP00016) 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:curcumin) decreases a(HBP:HBP00016) View Subject | View Object

Pro-autophagic effects of curcumin are reflected in improved function in cellular and animal models of PD and AD, as well as reduced levels of α-synuclein aggregates 144 or Aβ and tau oligomers 145,146 . PubMed:30116051

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

a(CHEBI:geldanamycin) decreases a(HBP:HBP00016) View Subject | View Object

Among compounds that inhibit HSP90, geldanamycin promoted elimination of both hyper- phosphorylated tau and oligomeric α-synuclein in cell lines 219,220 . PubMed:30116051

Appears in Networks:

a(CHEBI:tanespimycin) decreases a(HBP:HBP00016) View Subject | View Object

The less cytotoxic analogue of geldanamycin, 17-AAG, has improved brain penetrance. It decreased Aβ levels 223 , improved memory 224 and lowered tau in transgenic AD mice 224 . 17-AAG also reduced α-synuclein oligomers in H4 cells 220 . PubMed:30116051

Appears in Networks:

a(PUBCHEM:129688311) decreases a(HBP:HBP00016) View Subject | View Object

Harnessing TFEB by 2-hydroxypropyl-β-cyclodextrin promoted clearance of proteolipid aggregates and α-syn- uclein in a cellular model of PD 195,204 .It also augmented the elimination of Aβ in a Tg19959/CRND8 mouse model of AD 173 . PubMed:30116051

Appears in Networks:
Annotations
MeSH
Parkinson Disease

p(HGNC:GBA, var("?")) increases a(HBP:HBP00016) View Subject | View Object

Fourth, homozygous mutations of lyso- somal β-glucocerebrosidase (βGCase; also known as GBA) provoke the LSD Gaucher disease, which is linked to decreased ALN flux, α-synuclein accumulation and a fivefold increase in risk of PD 43 (Supplementary Box 1). PubMed:30116051

Appears in Networks:
Annotations
MeSH
Parkinson Disease

p(HGNC:IDE) decreases a(HBP:HBP00016) View Subject | View Object

Aβ42 and amylin (a pancreas-derived, AD-associated protein found in brain) are substrates for degradation by IDE, which also irreversibly traps Aβ42 and α-synuclein, preventing their aggregation and promoting ALN and UPS elimination 259 . PubMed:30116051

Appears in Networks:

Out-Edges 5

a(HBP:HBP00016) increases path(MESH:"Parkinson Disease") View Subject | View Object

Not only did this discovery draw attention to aggregated forms of a-syn as mediators of Parkinson’s disease pathogenesis, but also opened the door to the use of a-syn detection techniques for diagnosis and staging. PubMed:28803412

Appears in Networks:
Annotations
Confidence
Medium

a(HBP:HBP00016) positiveCorrelation path(MESH:"Parkinson Disease") View Subject | View Object

Parkinson’s disease (PD), Multiple System Atrophy (MSA) and Dementia with Lewy Bodies (DLB) are devastating synucleinopathies. The deposition of filamentous insoluble protein inclusions termed Lewy bodies and Lewy neurites whose main constituent is aggregated α -synuclein (α -syn) characterizes synucleinopathies. PubMed:27075649

Appears in Networks:
Annotations
Confidence
High
MeSH
Lewy Bodies

a(HBP:HBP00016) positiveCorrelation path(MESH:"Multiple System Atrophy") View Subject | View Object

Parkinson’s disease (PD), Multiple System Atrophy (MSA) and Dementia with Lewy Bodies (DLB) are devastating synucleinopathies. The deposition of filamentous insoluble protein inclusions termed Lewy bodies and Lewy neurites whose main constituent is aggregated α -synuclein (α -syn) characterizes synucleinopathies. PubMed:27075649

Appears in Networks:
Annotations
Confidence
High
MeSH
Lewy Bodies

a(HBP:HBP00016) positiveCorrelation path(MESH:"Lewy Body Disease") View Subject | View Object

Parkinson’s disease (PD), Multiple System Atrophy (MSA) and Dementia with Lewy Bodies (DLB) are devastating synucleinopathies. The deposition of filamentous insoluble protein inclusions termed Lewy bodies and Lewy neurites whose main constituent is aggregated α -synuclein (α -syn) characterizes synucleinopathies. PubMed:27075649

Appears in Networks:
Annotations
Confidence
High
MeSH
Lewy Bodies

a(HBP:HBP00016) decreases complex(GO:"proteasome complex") View Subject | View Object

Sixth, aggregates and mutant forms of α-synuclein disrupt the proteasome in dopaminergic neurons. PubMed:30116051

Appears in Networks:
Annotations
MeSH
Dopaminergic Neurons
MeSH
Parkinson Disease

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.