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This research was funded by Fondation de France, Agence Nationale de la Recherche, Grant PID2019-105136RB-100; Ministry of Science and Innovation (MICINN); and European Regional Development Fund (ERDF), EU.

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Article

Increased Expression of Alpha-, Beta-, and Gamma-Synucleins in Brainstem Regions of a Non-Human Primate Model of Parkinson's Disease

Publicated to:International Journal Of Molecular Sciences. 23 (15): 8586- - 2022-08-01 23(15), DOI: 10.3390/ijms23158586

Authors: Duperrier, S; Sgambato, V; Bortolozzi, A

Affiliations

CNRS, Inst Sci Cognit Marc Jeannerod ISCMJ, Unite Mixte Rech 5229, F-69675 Bron, France - Author
CSIC, August Pi i Sunyer Biomed Res Inst IDIBAPS, Inst Invest Biomed Barcelona IIBB, Barcelona 08036, Spain - Author
Inst Hlth Carlos III ISCIII, Biomed Res Networking Ctr Mental Hlth CIBERSAM, Madrid 28029, Spain - Author
Univ Claude Bernard 1, UFR Biosci, F-69100 Villeurbanne, France - Author

Abstract

Parkinson's disease (PD) is characterized by cell loss in the substantia nigra and the presence of alpha-synuclein (alpha-syn)-containing neuronal Lewy bodies. While alpha-syn has received major interest in the pathogenesis of PD, the function of beta- and gamma-synucleins (beta-syn and gamma-syn, respectively) is not really known. Yet, these proteins are members of the same family and also concentrated in neuronal terminals. The current preclinical study investigated the expression levels of alpha-, beta-, and gamma-synucleins in brainstem regions involved in PD physiopathology. We analyzed synuclein expression in the substantia nigra, raphe nuclei, pedunculopontine nucleus, and locus coeruleus from control and parkinsonian (by MPTP) macaques. MPTP-intoxicated monkeys developed a more or less severe parkinsonian score and were sacrificed after a variable post-MPTP period ranging from 1 to 20 months. The expression of the three synucleins was increased in the substantia nigra after MPTP, and this increase correlates positively, although not very strongly, with cell loss and motor score and not with the time elapsed after intoxication. In the dorsal raphe nucleus, the expression of the three synucleins was also increased, but only alpha- and gamma-Syn are linked to the motor score and associated cell loss. Finally, although no change in synuclein expression was demonstrated in the locus coeruleus after MPTP, we found increased expression levels of gamma-Syn, which are only correlated with cell loss in the pedunculopontine nucleus. Altogether, our data suggest that these proteins may play a key role in brainstem regions and mesencephalic tegmentum. Given the involvement of these brain regions in non-motor symptoms of PD, these data also strengthen the relevance of the MPTP macaque model of PD, which exhibits pathological changes beyond nigral DA cell loss and alpha-synucleinopathy.

Keywords
alpha-synucleinbeta-synucleincholinergic neuronsdopaminergic-neuronsgamma-synucleinlewy bodymptpnervous-systemnon-motor symptomspathologypedunculopontine nucleuspreferential losssubstantia-nigra1,2,3,6 tetrahydro 1 methyl 4 phenylpyridine1-methyl-4-phenyl-1,2,3,6-tetrahydropyridineAlpha synucleinAlpha-synucleinAnimalAnimalsBeta-synucleinBrain stemGamma synucleinGamma-synucleinGeneticsLocus-coeruleusMetabolismMptpNon-motor symptomsParkinson diseaseParkinson's diseaseParkinson’s diseasePrimatePrimatesSubstantia nigra

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal International Journal Of Molecular Sciences 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 66/285, thus managing to position itself as a Q1 (Primer Cuartil), in the category Biochemistry & Molecular Biology.

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: 2.65, 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 2025-05-11, the following number of citations:

  • WoS: 8
  • Scopus: 11
  • Europe PMC: 5
  • OpenCitations: 7
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 2025-05-11:

  • 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: 23.
  • 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: 22 (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: 11.6.
  • The number of mentions on the social network X (formerly Twitter): 4 (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: France.