Evidence map›Paper›PMID 27636528›Full record

ArticleJournal of psychiatry & neuroscience : JPN2017

The proof-of-concept of ASS234: Peripherally administered ASS234 enters the central nervous system and reduces pathology in a male mouse model of Alzheimer disease.

Mari Paz Serrano, Raquel Herrero-Labrador, Hunter S Futch, Julia Serrano, Alejandro Romero, Ana Patricia Fernandez, Abdelouahid Samadi, Mercedes Unzeta, Jose Marco-Contelles, Ricardo Martínez-Murillo

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In one paragraph

Article in Journal of psychiatry & neuroscience : JPN, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
4.6field-weighted citation impact, top 6% 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

  1. Pooled it
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  3. Review
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  5. Review
  6. ACS chemical neuroscience · 2020
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  7. Review
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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

10 authors at 5 institutions in 3 countries.

Mari Paz SerranoFrom the Neurovascular Research Group, Department of Translational Neurobiology, Cajal Institute (CSIC), Madrid, Spain (Serrano, Herrero-Labrador, Serrano, Fernandez, Martínez-Murillo); the Departament of Toxicology and Pharmacology, School of Veterinary, Complutense University of Madrid, Madrid, Spain (Romero); the Laboratory of Medicinal Chemistry, Institute of Organic Chemistry (CSIC), Madrid, Spain (Marco-Contelles); the College of Medicine, University of Florida, Gainesville, Florida. USA (Futch); the Departament de Bioquímica i Biología Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain (Unzeta); and the Department of Chemistry, United Arab Emirates University, Abu Dhabi, United Arab Emirates (Samadi).
Raquel Herrero-LabradorFrom the Neurovascular Research Group, Department of Translational Neurobiology, Cajal Institute (CSIC), Madrid, Spain (Serrano, Herrero-Labrador, Serrano, Fernandez, Martínez-Murillo); the Departament of Toxicology and Pharmacology, School of Veterinary, Complutense University of Madrid, Madrid, Spain (Romero); the Laboratory of Medicinal Chemistry, Institute of Organic Chemistry (CSIC), Madrid, Spain (Marco-Contelles); the College of Medicine, University of Florida, Gainesville, Florida. USA (Futch); the Departament de Bioquímica i Biología Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain (Unzeta); and the Department of Chemistry, United Arab Emirates University, Abu Dhabi, United Arab Emirates (Samadi).
Hunter S FutchFrom the Neurovascular Research Group, Department of Translational Neurobiology, Cajal Institute (CSIC), Madrid, Spain (Serrano, Herrero-Labrador, Serrano, Fernandez, Martínez-Murillo); the Departament of Toxicology and Pharmacology, School of Veterinary, Complutense University of Madrid, Madrid, Spain (Romero); the Laboratory of Medicinal Chemistry, Institute of Organic Chemistry (CSIC), Madrid, Spain (Marco-Contelles); the College of Medicine, University of Florida, Gainesville, Florida. USA (Futch); the Departament de Bioquímica i Biología Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain (Unzeta); and the Department of Chemistry, United Arab Emirates University, Abu Dhabi, United Arab Emirates (Samadi).
Julia SerranoFrom the Neurovascular Research Group, Department of Translational Neurobiology, Cajal Institute (CSIC), Madrid, Spain (Serrano, Herrero-Labrador, Serrano, Fernandez, Martínez-Murillo); the Departament of Toxicology and Pharmacology, School of Veterinary, Complutense University of Madrid, Madrid, Spain (Romero); the Laboratory of Medicinal Chemistry, Institute of Organic Chemistry (CSIC), Madrid, Spain (Marco-Contelles); the College of Medicine, University of Florida, Gainesville, Florida. USA (Futch); the Departament de Bioquímica i Biología Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain (Unzeta); and the Department of Chemistry, United Arab Emirates University, Abu Dhabi, United Arab Emirates (Samadi).
Alejandro RomeroFrom the Neurovascular Research Group, Department of Translational Neurobiology, Cajal Institute (CSIC), Madrid, Spain (Serrano, Herrero-Labrador, Serrano, Fernandez, Martínez-Murillo); the Departament of Toxicology and Pharmacology, School of Veterinary, Complutense University of Madrid, Madrid, Spain (Romero); the Laboratory of Medicinal Chemistry, Institute of Organic Chemistry (CSIC), Madrid, Spain (Marco-Contelles); the College of Medicine, University of Florida, Gainesville, Florida. USA (Futch); the Departament de Bioquímica i Biología Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain (Unzeta); and the Department of Chemistry, United Arab Emirates University, Abu Dhabi, United Arab Emirates (Samadi).
Ana Patricia FernandezFrom the Neurovascular Research Group, Department of Translational Neurobiology, Cajal Institute (CSIC), Madrid, Spain (Serrano, Herrero-Labrador, Serrano, Fernandez, Martínez-Murillo); the Departament of Toxicology and Pharmacology, School of Veterinary, Complutense University of Madrid, Madrid, Spain (Romero); the Laboratory of Medicinal Chemistry, Institute of Organic Chemistry (CSIC), Madrid, Spain (Marco-Contelles); the College of Medicine, University of Florida, Gainesville, Florida. USA (Futch); the Departament de Bioquímica i Biología Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain (Unzeta); and the Department of Chemistry, United Arab Emirates University, Abu Dhabi, United Arab Emirates (Samadi).
Abdelouahid SamadiFrom the Neurovascular Research Group, Department of Translational Neurobiology, Cajal Institute (CSIC), Madrid, Spain (Serrano, Herrero-Labrador, Serrano, Fernandez, Martínez-Murillo); the Departament of Toxicology and Pharmacology, School of Veterinary, Complutense University of Madrid, Madrid, Spain (Romero); the Laboratory of Medicinal Chemistry, Institute of Organic Chemistry (CSIC), Madrid, Spain (Marco-Contelles); the College of Medicine, University of Florida, Gainesville, Florida. USA (Futch); the Departament de Bioquímica i Biología Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain (Unzeta); and the Department of Chemistry, United Arab Emirates University, Abu Dhabi, United Arab Emirates (Samadi).
Mercedes UnzetaFrom the Neurovascular Research Group, Department of Translational Neurobiology, Cajal Institute (CSIC), Madrid, Spain (Serrano, Herrero-Labrador, Serrano, Fernandez, Martínez-Murillo); the Departament of Toxicology and Pharmacology, School of Veterinary, Complutense University of Madrid, Madrid, Spain (Romero); the Laboratory of Medicinal Chemistry, Institute of Organic Chemistry (CSIC), Madrid, Spain (Marco-Contelles); the College of Medicine, University of Florida, Gainesville, Florida. USA (Futch); the Departament de Bioquímica i Biología Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain (Unzeta); and the Department of Chemistry, United Arab Emirates University, Abu Dhabi, United Arab Emirates (Samadi).
Jose Marco-ContellesFrom the Neurovascular Research Group, Department of Translational Neurobiology, Cajal Institute (CSIC), Madrid, Spain (Serrano, Herrero-Labrador, Serrano, Fernandez, Martínez-Murillo); the Departament of Toxicology and Pharmacology, School of Veterinary, Complutense University of Madrid, Madrid, Spain (Romero); the Laboratory of Medicinal Chemistry, Institute of Organic Chemistry (CSIC), Madrid, Spain (Marco-Contelles); the College of Medicine, University of Florida, Gainesville, Florida. USA (Futch); the Departament de Bioquímica i Biología Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain (Unzeta); and the Department of Chemistry, United Arab Emirates University, Abu Dhabi, United Arab Emirates (Samadi).
Ricardo Martínez-MurilloFrom the Neurovascular Research Group, Department of Translational Neurobiology, Cajal Institute (CSIC), Madrid, Spain (Serrano, Herrero-Labrador, Serrano, Fernandez, Martínez-Murillo); the Departament of Toxicology and Pharmacology, School of Veterinary, Complutense University of Madrid, Madrid, Spain (Romero); the Laboratory of Medicinal Chemistry, Institute of Organic Chemistry (CSIC), Madrid, Spain (Marco-Contelles); the College of Medicine, University of Florida, Gainesville, Florida. USA (Futch); the Departament de Bioquímica i Biología Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain (Unzeta); and the Department of Chemistry, United Arab Emirates University, Abu Dhabi, United Arab Emirates (Samadi).
Universidad Complutense de Madrid · ESInstituto de Química Orgánica General · ESUnited Arab Emirates University · AEUniversitat Autònoma de Barcelona · ESUniversity of Florida · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe heterogeneity of Alzheimer disease requires the development of multitarget drugs for treating the symptoms of the disease and its progression. Both cholinergic and monoamine oxidase dysfunctions are involved in the pathological process. Thus, we hypothesized that the development of therapies focused on these targets might be effective. We have developed and assessed a new product, coded ASS234, a multipotent acetyl and butyrylcholinesterase/monoamine oxidase A-B inhibitor with a potent inhibitory effect on amyloid-β aggregation as well as antioxidant and antiapoptotic properties. But there is a need to reliably correlate in vitro and in vivo drug release data.

methodsWe examined the effect of ASS234 on cognition in healthy adult C57BL/6J mice in a model of scopolamine-induced cognitive impairment that often accompanies normal and pathological aging. Also, in a characterized transgenic APPswe/PS1ΔE9 mouse model of Alzheimer disease, we examined the effects of short-term ASS234 treatment on plaque deposition and gliosis using immunohistochemistry. Toxicology of ASS234 was assessed using a quantitative high-throughput in vitro cytotoxicity screening assay following the MTT assay method in HepG2 liver cells.

resultsIn vivo, ASS234 significantly decreased scopolamine-induced learning deficits in C57BL/6J mice. Also, reduction of amyloid plaque burden and gliosis in the cortex and hippocampus was assessed. In vitro, ASS234 exhibited lesser toxicity than donepezil and tacrine. LIMITATIONS: The study was conducted in male mice only. Although the Alzheimer disease model does not recapitulate all features of the human disease, it exhibits progressive monoaminergic neurodegeneration.

conclusionASS234 is a promising alternative drug of choice to treat the cognitive decline and neurodegeneration underlying Alzheimer disease.

Indexed as

Alzheimer DiseaseAnimalsCell SurvivalCerebral CortexDisease Models, AnimalDonepezilGliosisHep G2 CellsHippocampusHumansIndansIndolesLearningMaleMice, Inbred C57BLNootropic AgentsDonepezilIndansIndolesN-((5-(3-(1-benzylpiperidin-4-yl)propoxy)-1-methyl-1H-indol-2-yl)methyl)-N-methylprop-2-yn-1-amineNootropic AgentsPiperidinesScopolamineTacrine

Identifiers

PMID27636528
PMCPMC5373713
OpenAlexW2523413541

What OpenQuestion holds

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Registered trials

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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.