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Garcia-Gimeno, MaAuthor

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October 30, 2024
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Neuroprotective Effect of IND1316, an Indole-Based AMPK Activator, in Animal Models of Huntington Disease

Publicated to:Acs Chemical Neuroscience. 13 (2): 275-287 - 2022-01-19 13(2), DOI: 10.1021/acschemneuro.1c00758

Authors: Vela, Marta; Garcia-Gimeno, Maria Adelaida; Sanchis, Ana; Bono-Yague, Jose; Cumella, Jose; Lagartera, Laura; Perez, Concepcion; Priego, Eva-Maria; Campos, Angela; Sanz, Pascual; Vazquez-Manrique, Rafael P; Castro, Ana

Affiliations

Ctr Invest Biomed Red Enfermedades Raras CIBERER - Author
IBV CSIC, Inst Biomed Valencia - Author
IQM CSIC, Inst Quim Med - Author
Joint Unit Rare Dis IIS La Fe CIPF - Author
Univ Politecn Valencia, Dept Biotechnol, Escuela Tecn Super Ingn Agron & Medio Nat ETSIAMN - Author
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Abstract

Aggregation of mutant huntingtin, because of an expanded polyglutamine track, underlies the cause of neurodegeneration in Huntington disease (HD). However, it remains unclear how some alterations at the cellular level lead to specific structural changes in HD brains. In this context, the neuroprotective effect of the activation of AMP-activated protein kinase (AMPK) appears to be a determinant factor in several neurodegenerative diseases, including HD. In the present work, we describe a series of indole-derived compounds able to activate AMPK at the cellular level. By using animal models of HD (both worms and mice), we demonstrate the in vivo efficacy of one of these compounds (IND1316), confirming that it can reduce the neuropathological symptoms of this disease. Taken together, in vivo results and in silico studies of druggability, allow us to suggest that IND1316 could be considered as a promising new lead compound for the treatment of HD and other central nervous system diseases in which the activation of AMPK results in neuroprotection.

Keywords

6,7 dihydro 4 hydroxy 3 (2' hydroxy 1,1' biphenyl 4 yl) 6 oxothieno[2,3 b]pyridine 5 carbonitrileAdme in silicoAdultAmp-activated protein kinasesAmpkAnimalAnimal experimentAnimal modelAnimalsArticleBenzyl derivativeBlood brain barrierC. elegans modelsCellCentral nervous system diseaseChaperoneComparative studyControlled studyDisease modelDisease models, animalDrug bioavailabilityDysfunctionEnhancementEnzyme phosphorylationExpressionGeneticsHek293 cell lineHuntingtinHuntingtin proteinHuntington choreaHuntington diseaseHuntington disease mouse modelsHydroxymethylglutaryl coenzyme a reductase kinaseIn vivo studyInd 1316Indole derivativeIndole derivativesIndolesInterleukin 1betaMaleMdck cell lineMechanosensingMiceMouseNeuroprotectionNeuroprotective agentNeuroprotective agentsNonhumanOral absorptionPhenforminPhenotypePolyq aggregationPolyq toxicityPromotesProtein-kinaseStructure activity relationSurface plasmon resonanceTail suspension testToxicityTumor necrosis factorUnclassified drugWater solubilityWestern blotting

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Acs Chemical Neuroscience due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Medicine (Miscellaneous).

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 2025-07-19:

  • WoS: 5
  • Scopus: 5

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 2025-07-19:

  • 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: 18.
  • 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: 21 (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: 19.7.
  • The number of mentions on the social network X (formerly Twitter): 15 (Altmetric).
  • The number of mentions in news outlets: 1 (Altmetric).