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Analysis of institutional authors

Hernandez Perez, FelixAuthorCastro MAuthorHernández IhAuthorElorza AAuthorPerez BAuthorLopez-Sendon JlAuthor

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October 25, 2021
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CPEB alteration and aberrant transcriptome-polyadenylation lead to a treatable SLC19A3 deficiency in Huntington’s disease

Publicated to:Science Translational Medicine. 13 (613): eabe7104- - 2021-09-29 13(613), DOI: 10.1126/scitranslmed.abe7104

Authors: Pico, Sara; Parras, Alberto; Santos-Galindo, Maria; Pose-Utrilla, Julia; Castro, Margarita; Fraga, Enrique; Hernandez, Ivo H; Elorza, Ainara; Anta, Hector; Wang, Nan; Marti-Sanchez, Laura; Belloc, Eulalia; Garcia-Esparcia, Paula; Garrido, Juan J; Ferrer, Isidro; Macias-Garcia, Daniel; Mir, Pablo; Artuch, Rafael; Perez, Belen; Hernandez, Felix; Navarro, Pilar; Luis Lopez-Sendon, Jose; Iglesias, Teresa; Yang, X William; Mendez, Raul; Lucas, Jose J

Affiliations

Barcelona Inst Sci & Technol, Inst Res Biomed IRB, Barcelona 08028, Spain - Author
CIBER Enfermedades Neurodegenerativas , Consejo Superior de Investigaciones Científicas - Author
CIBER Enfermedades Neurodegenerativas , CSIC - Instituto Cajal (IC) - Author
CIBER Enfermedades Neurodegenerativas , CSIC-UAM - Centro de Biología Molecular Severo Ochoa (CBM) - Author
CIBER Enfermedades Neurodegenerativas , CSIC-UAM - Centro de Biología Molecular Severo Ochoa (CBM) , Centro Nacional de Investigaciones Cardiovasculares Carlos III - Author
CIBER Enfermedades Neurodegenerativas , Hospital Universitari de Bellvitge - Author
CIBER Enfermedades Neurodegenerativas , Hospital Universitario Virgen del Rocío - Author
CIBER Enfermedades Neurodegenerativas , Universidad Autónoma de Madrid , CSIC-UAM - Centro de Biología Molecular Severo Ochoa (CBM) - Author
CSIC UAM, Ctr Mol Biol Severo Ochoa CBMSO, Madrid 28049, Spain - Author
CSIC-UAM - Centro de Biología Molecular Severo Ochoa (CBM) , Instituto de Salud Carlos III , Centro de Diagnóstico de Enfermedades Moleculares (CEDEM) - Author
Ctr Diagnost Enfermedades Moleculares CEDEM, Madrid 28049, Spain - Author
Ctr Nacl Invest Cardiovasc CNIC, Madrid 28029, Spain - Author
Hosp Mar Med Res Inst IMIM, Unidad Asociada I D I IMIM IIBB CSIC, Canc Res Program, Barcelona 08003, Spain - Author
Hosp Ramon & Cajal, Inst Ramon Y Cajal Invest Sanitaria IRYCIS, Dept Neurol, Madrid 28034, Spain - Author
Hospital del Mar , Institut d'Investigacions Biomèdiques August Pi i Sunyer - IDIBAPS , Consejo Superior de Investigaciones Científicas - Author
Hospital del Mar , IRB Barcelona - Institute for Research in Biomedicine - Author
Hospital Ramón y Cajal - Author
Inst Biomed Res Barcelona IIBB CSIC, Barcelona 08036, Spain - Author
Inst Cajal CSIC, Dept Mol Cellular & Dev Neurobiol, Madrid 28002, Spain - Author
Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona 08010, Spain - Author
Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona 08036, Spain - Author
Inst Recerca St Joan de Deu, Dept Clin Biochem, Barcelona 08950, Spain - Author
Inst Salud Carlos III, Networking Res Ctr Neurodegenerat Dis CIBERNED, Madrid 28031, Spain - Author
Institució Catalana de Recerca i Estudis Avançats , IRB Barcelona - Institute for Research in Biomedicine - Author
Instituto de Salud Carlos III , Institut de Recerca Sant Joan de Déu - Author
IRB Barcelona - Institute for Research in Biomedicine - Author
ISCIII, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid 28029, Spain - Author
Jane & Terry Semel Institute for Neuroscience & Human Behavior - Author
Univ Autonoma Madrid CSIC UAM, Inst Invest Biomed Alberto Sols, Consejo Super Invest Cient, Madrid 28029, Spain - Author
Univ Autonoma Madrid, Fac Ciencias, Dept Biol, Unidad Docente Fisiol Anim, Madrid 28049, Spain - Author
Univ Barcelona, IDIBELL Univ Hosp Bellvitge, Inst Neuropathol, Barcelona 08908, Spain - Author
Univ Calif Los Angeles, David Geffen Sch Med, Jane & Terry Semel Inst Neurosci & Human Behav, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA - Author
Univ Seville, Inst Biomed Sevilla IBiS, Serv Neurol & Neurofisiol Clin, Unidad Trastornos Movimiento,CSIC,Hosp Univ Virge, Seville 41013, Spain - Author
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Abstract

Huntington’s disease (HD) is a hereditary neurodegenerative disorder of the basal ganglia for which disease-modifying treatments are not yet available. Although gene-silencing therapies are currently being tested, further molecular mechanisms must be explored to identify druggable targets for HD. Cytoplasmic polyadenylation element binding proteins 1 to 4 (CPEB1 to CPEB4) are RNA binding proteins that repress or activate translation of CPE-containing transcripts by shortening or elongating their poly(A) tail. Here, we found increased CPEB1 and decreased CPEB4 protein in the striatum of patients and mouse models with HD. This correlated with a reprogramming of polyadenylation in 17.3% of the transcriptome, markedly affecting neurodegeneration-associated genes including PSEN1, MAPT, SNCA, LRRK2, PINK1, DJ1, SOD1, TARDBP, FUS, and HTT and suggesting a new molecular mechanism in neurodegenerative disease etiology. We found decreased protein content of top deadenylated transcripts, including striatal atrophy–linked genes not previously related to HD, such as KTN1 and the easily druggable SLC19A3 (the ThTr2 thiamine transporter). Mutations in SLC19A3 cause biotin-thiamine–responsive basal ganglia disease (BTBGD), a striatal disorder that can be treated with a combination of biotin and thiamine. Similar to patients with BTBGD, patients with HD demonstrated decreased thiamine in the cerebrospinal fluid. Furthermore, patients and mice with HD showed decreased striatal concentrations of thiamine pyrophosphate (TPP), the metabolically active form of thiamine. High-dose biotin and thiamine treatment prevented TPP deficiency in HD mice and attenuated the radiological, neuropathological, and motor HD-like phenotypes, revealing an easily implementable therapy that might benefit patients with HD.

Keywords

Cpeb1 protein, humanHumansHuntington diseaseMembrane transport proteinsMrna cleavage and polyadenylation factorsPolyadenylationSlc19a3 protein, humanTranscription factorsTranscriptome

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Science Translational Medicine 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, 2021, it was in position 3/139, thus managing to position itself as a Q1 (Primer Cuartil), in the category Medicine, Research & Experimental. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.15. This 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:

  • Weighted Average of Normalized Impact by the Scopus agency: 1.57 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 3.74 (source consulted: Dimensions Jul 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-07-09, the following number of citations:

  • WoS: 11
  • Scopus: 14
  • Europe PMC: 9

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 2025-07-09:

  • 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: 33.
  • 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: 35 (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: 97.95.
  • The number of mentions on the social network X (formerly Twitter): 69 (Altmetric).
  • The number of mentions in news outlets: 6 (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.

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: 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 (Picó S) and Last Author (Lucas JJ).