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Analysis of institutional authors

Mari Ayala, MartaAuthorRoca-Agujetas VAuthorDe Dios CAuthorPodlesniy PAuthorAbadin XAuthorMorales AAuthorMari MAuthorTrullas RAuthorColell ACorresponding Author
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Cholesterol alters mitophagy by impairing optineurin recruitment and lysosomal clearance in Alzheimer’s disease

Publicated to:Molecular Neurodegeneration. 16 (1): 15- - 2021-03-08 16(1), DOI: 10.1186/s13024-021-00435-6

Authors: Roca-Agujetas, Vicente; Barbero-Camps, Elisabet; de Dios, Cristina; Podlesniy, Petar; Abadin, Xenia; Morales, Albert; Mari, Montserrat; Trullas, Ramon; Colell, Anna

Affiliations

CIBER Enfermedades Neurodegenerativas - Author
Institut d'Investigacions Biomèdiques August Pi i Sunyer - IDIBAPS - Author
Universitat de Barcelona - Author
‎ Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain - Author
‎ Inst Invest Biomed August Pi & Sunyer IDIBAPS, Consejo Super Invest Cient CSIC, Inst Invest Biomed Barcelona IIBB, Dept Cell Death & Proliferat, C Rossello 161,6th Floor, Barcelona 08036, Spain - Author
‎ Inst Invest Biomed August Pi & Sunyer IDIBAPS, Inst Invest Biomed Barcelona IIBB, Neurobiol Unit, Consejo Super Invest Cient CSIC, Barcelona, Spain - Author
‎ Univ Barcelona, Fac Med, Dept Biomed, Barcelona, Spain - Author
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Abstract

© 2021, The Author(s). Background: Emerging evidence indicates that impaired mitophagy-mediated clearance of defective mitochondria is a critical event in Alzheimer’s disease (AD) pathogenesis. Amyloid-beta (Aβ) metabolism and the microtubule-associated protein tau have been reported to regulate key components of the mitophagy machinery. However, the mechanisms that lead to mitophagy dysfunction in AD are not fully deciphered. We have previously shown that intraneuronal cholesterol accumulation can disrupt the autophagy flux, resulting in low Aβ clearance. In this study, we examine the impact of neuronal cholesterol changes on mitochondrial removal by autophagy. Methods: Regulation of PINK1-parkin-mediated mitophagy was investigated in conditions of acute (in vitro) and chronic (in vivo) high cholesterol loading using cholesterol-enriched SH-SY5Y cells, cultured primary neurons from transgenic mice overexpressing active SREBF2 (sterol regulatory element binding factor 2), and mice of increasing age that express the amyloid precursor protein with the familial Alzheimer Swedish mutation (Mo/HuAPP695swe) and mutant presenilin 1 (PS1-dE9) together with active SREBF2. Results: In cholesterol-enriched SH-SY5Y cells and cultured primary neurons, high intracellular cholesterol levels stimulated mitochondrial PINK1 accumulation and mitophagosomes formation triggered by Aβ while impairing lysosomal-mediated clearance. Antioxidant recovery of cholesterol-induced mitochondrial glutathione (GSH) depletion prevented mitophagosomes formation indicating mitochondrial ROS involvement. Interestingly, when brain cholesterol accumulated chronically in aged APP-PSEN1-SREBF2 mice the mitophagy flux was affected at the early steps of the pathway, with defective recruitment of the key autophagy receptor optineurin (OPTN). Sustained cholesterol-induced alterations in APP-PSEN1-SREBF2 mice promoted an age-dependent accumulation of OPTN into HDAC6-positive aggresomes, which disappeared after in vivo treatment with GSH ethyl ester (GSHee). The analyses in post-mortem brain tissues from individuals with AD confirmed these findings, showing OPTN in aggresome-like structures that correlated with high mitochondrial cholesterol levels in late AD stages. Conclusions: Our data demonstrate that accumulation of intracellular cholesterol reduces the clearance of defective mitochondria and suggest recovery of the cholesterol homeostasis and the mitochondrial scavenging of ROS as potential therapeutic targets for AD.

Keywords
aggressomesapp-psen1 miceglutathionemitochondriaoptineurinoxidative stressparkinpink1AggressomesAlzheimer diseaseAmyloid beta-peptidesAmyloid beta-protein precursorAnimalsApp-psen1 miceAutophagyCholesterolGlutathioneLysosomesMice, transgenicMitochondriaNeuronsOptineurinOxidative stressParkinParkin proteinPink1Ubiquitin-protein ligases

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Molecular Neurodegeneration 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 7/275, 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 provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 4.08. 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: 3.23 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 11 (source consulted: Dimensions May 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-05-16, the following number of citations:

  • WoS: 59
  • Scopus: 63
  • Europe PMC: 38
  • Google Scholar: 4
  • OpenCitations: 51
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 2025-05-16:

  • 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: 97.
  • 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: 96 (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: 16.55.
  • The number of mentions on the social network X (formerly Twitter): 11 (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

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 (Roca Agujetas, Vicente) and Last Author (Colell Riera, Anna).

the author responsible for correspondence tasks has been Colell Riera, Anna.