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Serrano Mp, Herrero-Labrador R, Futch Hs, Serrano J, Romero A, Fernandez Ap, Samadi A, Unzeta M, Marco-Contelles J, Martínez-Murillo RAuthor

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January 1, 2017
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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

Publicated to: JOURNAL OF PSYCHIATRY & NEUROSCIENCE. 42 (1): 59-69 - 2017-01-01, DOI: 10.1503/jpn.150209

Authors:

Serrano MP; Herrero-Labrador R; Futch HS; Serrano J; Romero A; Fernandez AP; Samadi A; Unzeta M; Marco-Contelles J; Martínez-Murillo R
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Affiliations

College of Medicine, University of Florida, Gainesville, FL, United States - Author
Departament de Bioquímica i Biología Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain - Author
Departament of Toxicology and Pharmacology, School of Veterinary, Complutense University of Madrid, Madrid, Spain - Author
Department of Chemistry, United Arab Emirates University, Abu Dhabi, United Arab Emirates - Author
Laboratory of Medicinal Chemistry, Institute of Organic Chemistry (CSIC), Madrid, Spain - Author
Neurovascular Research Group, Department of Translational Neurobiology, Cajal Institute (CSIC), Madrid, Spain - Author
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Abstract

Background: The 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. Methods: We 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. Results: In 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. Conclusion: ASS234 is a promising alternative drug of choice to treat the cognitive decline and neurodegeneration underlying Alzheimer disease. © 2017 Joule Inc.
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Keywords

AdultAlzheimer diseaseAmyloid beta proteinAmyloid plaqueAnimalAnimal modelAnimal tissueAnimalsArticleAss234Brain cortexC57bl 6 mouseC57bl mouseCell survivalCell viability assayCentral nervous system agentsCerebral cortexChemistryControlled studyCytotoxicity assayDisease modelDisease models, animalDonepezilDrug effectsFluorescence microscopyGliosisHep g2 cellsHep-g2 cell lineHepatoma cellHigh throughput screeningHippocampusHumanHumansImmunohistochemistryIndan derivativeIndansIndole derivativeIndolesLearningMaleMetabolismMice, inbred c57blMouseMtt assayN-((5-(3-(1-benzylpiperidin-4-yl)propoxy)-1-methyl-1h-indol-2-yl)methyl)-n-methylprop-2-yn-1-amineNerve degenerationNonhumanNootropic agentNootropic agentsNovel object recognition testPathologyPiperidine derivativePiperidinesPlaque, amyloidProof of conceptProof of concept studyRecognitionRecognition (psychology)Scopolamine bromideScopolamine hydrobromideScopolamine-induced cognitive defectSingle drug doseTacrineUnclassified drug

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal JOURNAL OF PSYCHIATRY & NEUROSCIENCE due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2017, it was in position 13/142, thus managing to position itself as a Q1 (Primer Cuartil), in the category Psychiatry. Notably, the journal is positioned above the 90th percentile.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2026-11-12:

  • Scopus: 21
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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-11-12:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 76.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 78 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 1.
  • The number of mentions on the social network X (formerly Twitter): 1 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
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Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: United Arab Emirates; United States of America.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (HERRERO LABRADOR, RAQUEL) .

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