First-pass extracted concept

neurotoxic oligomeric species

Candidate: concept label1 source documents3 linked claims

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Aliases

oligomeric species, particular oligomeric intermediates

Extracted Explainers

What the tool is doing

This concept captures the small oligomeric intermediates proposed to arise along the polyQ aggregation pathway and to differ in neurotoxicity.

Source 1DOI PubMed

What problem it solves

It helps explain why aggregation-toxicity relationships may not be captured by counting only microscopically visible inclusions.

Source 1DOI PubMed

What it does not solve

The abstract does not identify a single definitive toxic oligomer species or a universal detection method.

Source 1DOI PubMed

Evidence Snippets

However, recent studies in which oligomeric species have been considered start to shed light on the identity of neurotoxic oligomeric species. Initial evidence suggests that conformational changes induced by polyQ expansions and their surrounding sequence lead to the formation of particular oligomeric intermediates that may differentially affect neurotoxicity.

Evidence 1Source 1DOI PubMedprovenance

Supporting Sources

Source 1review2010Acta NeuropathologicaDOI PubMed

1 evidence snippet 3 linked claims Claim 1 Claim 2 Claim 3

Linked Claims

Claim 1comparisonsupports2010Source 1DOI PubMed

Many prior studies focused on microscopically visible inclusion bodies, whereas considering oligomeric species may better illuminate the identity of neurotoxic species.

Quoted textsource-backed

Although many studies have investigated the relationship between polyQ aggregation and toxicity, these have mainly focussed on investigating changes in the formation of the classical hallmark of polyQ diseases, i.e. microscopically visible inclusion bodies. However, recent studies in which oligomeric species have been considered start to shed light on the identity of neurotoxic oligomeric species.

Claim 2mechanistic hypothesissupports2010Source 1DOI PubMed

PolyQ expansion-induced conformational changes and surrounding sequence context may drive formation of particular oligomeric intermediates with differential neurotoxicity.

Quoted textsource-backed

Initial evidence suggests that conformational changes induced by polyQ expansions and their surrounding sequence lead to the formation of particular oligomeric intermediates that may differentially affect neurotoxicity.

Claim 3mechanistic summarysupports2010Source 1DOI PubMed

Conformational changes of polyQ proteins relate to oligomerisation, aggregate morphology, and impaired cellular functions in vitro and in vivo.

Quoted textsource-backed

Here, we review what is known about conformations of polyQ peptides and proteins in their monomeric state from experimental and modelling data, how conformational changes of polyQ proteins relate to their oligomerisation and morphology of aggregates and which cellular function are impaired by oligomers, in vitro and in vivo.