{rfName}
Ca

Indexed in

License and use

Citations

156

Altmetrics

Analysis of institutional authors

Del Toro Ruiz, DanielAuthorAlberch, JAuthorPerez-Navarro, ECorresponding Author
Share
Publications
>
Article

Calcineurin is involved in the early activation of NMDA-mediated cell death in mutant huntingtin knock-in striatal cells

Publicated to:Journal Of Neurochemistry. 105 (5): 1596-1612 - 2008-06-01 105(5), DOI: 10.1111/j.1471-4159.2008.05252.x

Authors: Xifro, Xavier; Garcia-Martinez, Juan Manuel; del Toro, Daniel; Alberch, Jordi; Perez-Navarro, Esther

Affiliations

Institut d'Investigacions Biomèdiques August Pi i Sunyer - IDIBAPS - Author
Univ Barcelona, Fac Med, Dept Biol Cellular & Anat Patol, IDIBAPS,Ctr Invest Biomed Red Sobre Enfermedades, E-08036 Barcelona, Spain - Author

Abstract

Excitotoxicity has been proposed as one of the mechanisms involved in the specific loss of striatal neurons that occurs in Huntington's disease. Here, we studied the role of calcineurin in the vulnerability of striatal neurons expressing mutant huntingtin to excitotoxicity. To this end, we induced excitotoxicity by adding NMDA to a striatal precursor cell line expressing full-length wild-type (STHdh(Q7/Q7)) or mutant (STHdh(Q111/Q111)) huntingtin. We observed that cell death appeared earlier in STHdh(Q111/Q111) cells than in STHdh(Q7/Q7) cells. Interestingly, these former cells expressed higher levels of calcineurin A that resulted in a greater increase of its activity after NMDA receptor stimulation. Moreover, transfection of full-length mutant huntingtin in different striatal-derived cells (STHdh(Q7/Q7), M213 and primary cultures) increased calcineurin A protein levels. To determine whether high levels of calcineurin A might account for the earlier activation of cell death in mutant huntingtin knock-in cells, wild-type cells were transfected with calcineurin A. Calcineurin A-transfected STHdh(Q7/Q7) cells displayed a significant increase in cell death compared with that recorded in green fluorescent protein-transfected cells after NMDA treatment. Notably, addition of the calcineurin inhibitor FK-506 produced a more robust reduction in cell death in mutant huntingtin knock-in cells than it did in wild-type cells. These results suggest that high levels of calcineurin A could account for the increased vulnerability of striatal cells expressing mutant huntingtin to excitotoxicity.

Keywords
AnimalsCalcineurinCalpainCareCaspaseCell deathCell line, transformedCell survivalCells, culturedCorpus striatumDeath-associated protein kinaseExcitotoxicityFk-506Huntingtin proteinHuntington diseaseHuntington's diseaseMiceMice, inbred c57blMutationN-methylaspartateNerve tissue proteinsNeuronsNuclear proteinsSpain

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal Of Neurochemistry 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, 2008, it was in position 40/221, thus managing to position itself as a Q1 (Primer Cuartil), in the category Neurosciences.

From a relative perspective, and based on the normalized impact indicator calculated from the Field Citation Ratio (FCR) of the Dimensions source, it yields a value of: 3.48, 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: Dimensions May 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-05-20, the following number of citations:

  • WoS: 67
  • Scopus: 51
  • Europe PMC: 38
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 2025-05-20:

  • 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: 58 (PlumX).

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.
Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: MALDEN; United Kingdom.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: Last Author (Perez Navarro, Esther).

the author responsible for correspondence tasks has been Perez Navarro, Esther.