Evidence map›Paper›PMID 28475686›Full record

ArticleProtein engineering, design & selection : PEDS2017

Quercitrin and quercetin 3-β-d-glucoside as chemical chaperones for the A4V SOD1 ALS-causing mutant.

Philbert Ip, Priya Roy Sharda, Anna Cunningham, Sumon Chakrabartty, Vijay Pande, Avijit Chakrabartty

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Protein engineering, design & selection : PEDS, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 2 pooled it
2.5field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 43 citations in OpenAlex.

  1. Pooled it
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  4. International journal of molecular sciences · 2024
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  19. Chemical Chaperones Modulate the Formation of Metabolite Assemblies.International journal of molecular sciences · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 3 countries.

Philbert IpCampbell Family Institute for Cancer Research, Ontario Cancer Institute/University Health Network, Department of Biochemistry, University of Toronto, TMDT 4-305, 101 College Street, Toronto, Ontario, CanadaM5G 1L7.
Priya Roy ShardaCampbell Family Institute for Cancer Research, Ontario Cancer Institute/University Health Network, Department of Biochemistry, University of Toronto, TMDT 4-305, 101 College Street, Toronto, Ontario, CanadaM5G 1L7.
Anna CunninghamDepartment of Chemical and Systems Biology, School of Medicine, Stanford University, 269 Campus Drive, Stanford, CA, 94305-5174, USA.
Sumon ChakrabarttyCampbell Family Institute for Cancer Research, Ontario Cancer Institute/University Health Network, Department of Medical Biophysics, University of Toronto, TMDT 4-307, 101 College Street, Toronto, Ontario, CanadaM5G 1L7.
Vijay PandeDepartment of Chemistry, Stanford University, CA94305, USA.
Avijit ChakrabarttyCampbell Family Institute for Cancer Research, Ontario Cancer Institute/University Health Network, Department of Medical Biophysics, University of Toronto, TMDT 4-307, 101 College Street, Toronto, Ontario, CanadaM5G 1L7.
Cancer Institute (WIA) · INStanford University · USUniversity Health Network · CAUniversity of Toronto · CA

Funding

CIHR
6 · The paper itself

Abstract

In many cases of familial amyotrophic lateral sclerosis (ALS), mutant forms of the Cu,Zn superoxide dismutase protein (SOD1) misfold and aggregate in motor neurons. Monomers of the normally homodimeric SOD1 have been found in patient tissue, presymptomatic mouse models of ALS, and in vitro misfolding assays which suggests that monomerization might be an early step in the pathological SOD1 misfolding pathway. In this study, we targeted the dimer interface with small molecules that might act as chemical chaperones to stabilize the native dimer and prevent downstream misfolding and aggregation. We performed a computational screen with a library of ~4400 drugs and natural compounds that were docked to two pockets around the SOD1 dimer interface. Of the resultant hits, seven were tested for misfolding and aggregation inhibition activity with A4V mutant SOD1. Quercitrin, quercetin-3-β-d-glucoside (Q3BDG), and, to a markedly lesser extent, epigallocatechin gallate (EGCG) were found to combat misfolding and aggregation induced by hydrogen peroxide, a physiologically relevant stress, as assessed by a gel-based assay and 8-anilinonaphthalene-1-suflonic acid (ANS) fluorescence. Isothermal titration calorimetry (ITC) and a colourimetric assay determined that these molecules directly bind A4V SOD1. Based on these findings, we speculate that quercitrin and Q3BDG may be potential therapeutic inhibitors of misfolding and aggregation in SOD1-associated ALS.

Indexed as

Drug DiscoveryMolecular ChaperonesMolecular Docking SimulationMutationProtein FoldingQuercetinSuperoxide Dismutase-1Molecular ChaperonesQuercetinquercitrinSuperoxide Dismutase-1amyotrophic lateral sclerosischemical chaperonesCu,Zn superoxide dismutasenative-state stabilizersprotein misfolding

Identifiers

PMID28475686
PMCPMC5939853
OpenAlexW2610202041

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.