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PubMed: 27075649

Title
Structural and functional properties of prefibrillar α-synuclein oligomers.
Journal
Scientific reports
Volume
6
Issue
None
Pages
24526
Date
2016-04-14
Authors
Madiona K | Melki R | Pieri L

Evidence ce617c027f
JSON

The neurotransmitter dopamine (DA) has been shown to promote the formation of stable, SDS-resistant α -syn oligomers both in vitro and in neurons30–32 by different mechanisms, including the formation of stable α -syn-DA-quinone adducts, methionine oxidation, or non-covalent interactions33.

a(CHEBI:dopamine) increases a(HBP:HBP00093) View Subject | View Object

Appears in Networks:
Annotations
Cell Ontology (CL)
neuron
Confidence
High
MeSH
Lewy Bodies

Evidence 7ea1b865f3
JSON

DA-mediated α -syn oligomers constitute a range of SDS-resistant species with apparent molecular weights ranging from over 2200 to 200 kDa as determined by SEC (Fig. 4a).

a(CHEBI:dopamine) increases a(HBP:HBP00093) View Subject | View Object

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

Evidence e9362007b2
JSON

GA-cross-linked α -syn oligomers are also a heterogeneous set of SDS-resistant oligomeric species (Fig. 4b).

a(CHEBI:glutaraldehyde) increases a(HBP:HBP00093) View Subject | View Object

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

Evidence 76fdaa8003
JSON

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.

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

Appears in Networks:
Annotations
Confidence
High
MeSH
Lewy Bodies

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

Appears in Networks:
Annotations
Confidence
High
MeSH
Lewy Bodies

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

Appears in Networks:
Annotations
Confidence
High
MeSH
Lewy Bodies

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

Appears in Networks:
Annotations
Confidence
High
MeSH
Lewy Bodies

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

Appears in Networks:
Annotations
Confidence
High
MeSH
Lewy Bodies

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

Appears in Networks:
Annotations
Confidence
High
MeSH
Lewy Bodies

Evidence 631a556d08
JSON

1 nM (Fig. 3a, right panels and Fig. 3b, red curve, solid line) and 0.2 nM α -syn fibrils (Fig. 3b, red curve, dashed line) induced a progressive and significant increase of intracellular Ca2+ levels, as revealed by the rise of Fluo-4 fluorescence in exposed SH-SY5Y cells. In contrast, only a modest Ca2+ increase was observed in cells exposed to 300 nM on-fibrillar assembly pathway oligomeric α -syn (Fig. 3a, middle panels and Fig. 3b, blue curve, solid line) or 10 μM monomeric α -syn (Fig. 3a, left panels and Fig. 3b, black curve, solid line).

a(HBP:HBP00092) increases a(CHEBI:"calcium(2+)") View Subject | View Object

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

a(HBP:HBP00093) increases a(CHEBI:"calcium(2+)") View Subject | View Object

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

Evidence 1614b5a672
JSON

α -syn fibrils revealed to be highly toxic to cells at all the concentrations we tested, spanning 1 to 0.01 nM (53.4 ± 4% inhibition of MTT reduction at 0.01 nM, i.e. 0.1 μM equivalent monomer concentration) whereas α -syn oligomers only slightly impaired cell viability (23.9 ± 6% inhibition of MTT reduction at 300 nM, i.e. 10 μM initial monomer concentration) (Fig. 3c).

a(HBP:HBP00092) increases bp(GO:"apoptotic process") View Subject | View Object

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

a(HBP:HBP00093) increases bp(GO:"apoptotic process") View Subject | View Object

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

Evidence 612cee9420
JSON

Increasing amounts of fibrils and a concomitant decrease in the amount of oligomeric species were observed upon longer incubation times (Supplementary Fig. S1).

a(HBP:HBP00092) negativeCorrelation a(HBP:HBP00093) View Subject | View Object

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

a(HBP:HBP00093) negativeCorrelation a(HBP:HBP00092) View Subject | View Object

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

Evidence da00be6c92
JSON

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.

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

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

Evidence 5d6ae41337
JSON

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.

a(HBP:HBP00095) increases bp(GO:"neuron death") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Lewy Bodies

a(HBP:HBP00095) decreases bp(GO:"ion homeostasis") View Subject | View Object

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Lewy Bodies

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

Appears in Networks:
Annotations
Confidence
Medium
MeSH
Lewy Bodies

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