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Analysis of institutional authors

Giménez-Cassina A.AuthorDíaz-Nido J.Corresponding AuthorLoria F.Corresponding Author
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Article

The smoothened agonist SAG reduces mitochondrial dysfunction and neurotoxicity of frataxin-deficient astrocytes

Publicated to:Journal of Neuroinflammation. 19 (1): 93- - 2022-12-01 19(1), DOI: 10.1186/s12974-022-02442-w

Authors: Vicente-Acosta A; Giménez-Cassina A; Díaz-Nido J; Loria F

Affiliations

Ctr Biol Mol Severo Ochoa CSIC UAM, Nicolas Cabrera 1, Madrid 28049, Spain - Author
Hosp Univ Fdn Alcorcon, Lab Apoyo Invest, Budapest 1, Madrid 28922, Spain - Author
Hosp Univ Puerta de Hierro, Inst Invest Sanitaria Puerta de Hierro, Joaquin Rodrigo 1, Madrid 28222, Spain - Author
Univ Autonoma Madrid, Dept Biol Mol, Francisco Tomas & Valiente 7, Madrid 28049, Spain - Author
Univ Autonoma Madrid, Doctoral Sch, Program Mol Biosci, Madrid, Spain - Author
Universidad Autónoma de Madrid , CSIC-UAM - Centro de Biología Molecular Severo Ochoa (CBM) - Author
Universidad Autónoma de Madrid , CSIC-UAM - Centro de Biología Molecular Severo Ochoa (CBM) , Hospital Universitario Fundación Alcorcón - Author
Universidad Autónoma de Madrid , Hospital Universitario Puerta de Hierro Majadahonda , CSIC-UAM - Centro de Biología Molecular Severo Ochoa (CBM) - Author
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Abstract

Background: Friedreich’s ataxia is a rare hereditary neurodegenerative disease caused by decreased levels of the mitochondrial protein frataxin. Similar to other neurodegenerative pathologies, previous studies suggested that astrocytes might contribute to the progression of the disease. To fully understand the mechanisms underlying neurodegeneration in Friedreich’s ataxia, we investigated the reactivity status and functioning of cultured human astrocytes after frataxin depletion using an RNA interference-based approach and tested the effect of pharmacologically modulating the SHH pathway as a novel neuroprotective strategy. Results: We observed loss of cell viability, mitochondrial alterations, increased autophagy and lipid accumulation in cultured astrocytes upon frataxin depletion. Besides, frataxin-deficient cells show higher expression of several A1-reactivity markers and release of pro-inflammatory cytokines. Interestingly, most of these defects were prevented by chronically treating the cells with the smoothened agonist SAG. Furthermore, in vitro culture of neurons with conditioned medium from frataxin-deficient astrocytes results in a reduction of neuronal survival, neurite length and synapse formation. However, when frataxin-deficient astrocytes were chronically treated with SAG, we did not observe these alterations in neurons. Conclusions: Our results demonstrate that the pharmacological activation of the SHH pathway could be used as a target to modulate astrocyte reactivity and neuron–glia interactions to prevent neurodegeneration in Friedreich’s ataxia.

Keywords
frataxinmitochondrial dysfunctionneurotoxicityreactive astrocytessmoothened agonistFrataxinMitochondrial dysfunctionNeurotoxicityReactive astrocytesSmoothened agonistSonic hedgehog

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal of Neuroinflammation 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, 2022, it was in position 20/272, thus managing to position itself as a Q1 (Primer Cuartil), in the category Neurosciences. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations from Scopus Elsevier, it yields a value for the Field-Weighted Citation Impact from the Scopus agency: 1.36, which indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Field Citation Ratio (FCR) from Dimensions: 4.32 (source consulted: Dimensions May 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-05-13, the following number of citations:

  • WoS: 4
  • Scopus: 9
  • OpenCitations: 10
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 2025-05-13:

  • 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: 20.
  • 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: 20 (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: 13.55.
  • The number of mentions on the social network X (formerly Twitter): 19 (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.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: https://repositorio.uam.es/handle/10486/707128
Leadership analysis of institutional authors

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 (Vicente-Acosta A) and Last Author (LORIA SALINAS, FRIDA).

the authors responsible for correspondence tasks have been DIAZ NIDO, JAVIER and LORIA SALINAS, FRIDA.