Evidence map›Paper›PMID 22561309›Full record

ArticleMolecular and cellular neurosciences2012

A chemical genetic approach identifies piperazine antipsychotics as promoters of CNS neurite growth on inhibitory substrates.

Andrea L Johnstone, Gillian W Reierson, Robin P Smith, Jeffrey L Goldberg, Vance P Lemmon, John L Bixby

Abstract read
In one paragraph

Article in Molecular and cellular neurosciences, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.0field-weighted citation impact, top 29% 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

11 citing papers in PubMed, 30 citations in OpenAlex.

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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 2 institutions in 1 country.

Andrea L JohnstoneThe Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, 1400 NW 12th Ave, Miami, FL 33136, USA.
Gillian W Reierson
Robin P Smith
Jeffrey L Goldberg
Vance P Lemmon
John L Bixby
University of Miami · USNeurological Surgery · US

Funding

Shared Equipment ModuleP30EY014801 · NEI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Marco Ruggeri · 2004 to 2026
$12.2M
Novel Gene Targets for CNS Axonal RegenerationR01HD057632 · NICHD · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI BIXBY, JOHN L, LEMMON, VANCE P · 2007 to 2018
$4.7M
Kruppel-like Transcription Factors in Retinal Ganglion Cell RegenerationR01EY020913 · NEI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI GOLDBERG, JEFFREY L · 2010 to 2013
$2.2M
Novel Compounds That Overcome Glial Inhibition of Axonal RegenerationR01NS059866 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI BIXBY, JOHN L · 2009 to 2013
$1.7M
Triazine-based compounds to promote regeneration in optic neuropathiesU01NS074490 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI BIXBY, JOHN L, GOLDBERG, JEFFREY L · 2011 to 2012
$230k
Mechanisms Underlying Inhibition of Regeneration in CNS NeuronsF31NS063593 · NINDS · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI JOHNSTONE, ANDREA LYNN · 2008 to 2010
$76k
NEI NIH HHS P30 EY014801NEI NIH HHS P30EY014801NEI NIH HHS R01 EY020913NICHD NIH HHS R01 HD057632NICHD NIH HHS R01HD057632NINDS NIH HHS F31 NS063593NINDS NIH HHS F31NS063593NINDS NIH HHS R01 NS059866NINDS NIH HHS R01NS059866NINDS NIH HHS U01 NS074490NINDS NIH HHS U01NS074490
6 · The paper itself

Abstract

Injury to the central nervous system (CNS) can result in lifelong loss of function due in part to the regenerative failure of CNS neurons. Inhibitory proteins derived from myelin and the astroglial scar are major barriers for the successful regeneration of injured CNS neurons. Previously, we described the identification of a novel compound, F05, which promotes neurite growth from neurons challenged with inhibitory substrates in vitro, and promotes axonal regeneration in vivo (Usher et al., 2010). To identify additional regeneration-promoting compounds, we used F05-induced gene expression profiles to query the Broad Institute Connectivity Map, a gene expression database of cells treated with >1300 compounds. Despite no shared chemical similarity, F05-induced changes in gene expression were remarkably similar to those seen with a group of piperazine phenothiazine antipsychotics (PhAPs). In contrast to antipsychotics of other structural classes, PhAPs promoted neurite growth of CNS neurons challenged with two different glial derived inhibitory substrates. Our pharmacological studies suggest a mechanism whereby PhAPs promote growth through antagonism of calmodulin signaling, independent of dopamine receptor antagonism. These findings shed light on mechanisms underlying neurite-inhibitory signaling, and suggest that clinically approved antipsychotic compounds may be repurposed for use in CNS injured patients.

Indexed as

AnimalsAntipsychotic AgentsBrainCalcium SignalingCell Line, TumorCells, CulturedCHO CellsChondroitin Sulfate ProteoglycansCricetinaeCricetulusGene Expression ProfilingHumansNeuritesNeuronsOligonucleotide Array Sequence AnalysisPhenothiazinesAntipsychotic AgentsChondroitin Sulfate ProteoglycansPhenothiazinesPiperazines

Identifiers

PMID22561309
PMCPMC3383383
OpenAlexW2059393049

What OpenQuestion holds

Textmetadata
LicenceTDM
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.