Evidence map›Paper›PMID 38042807›Full record

ArticleCell death discovery2023

IGF2 prevents dopaminergic neuronal loss and decreases intracellular alpha-synuclein accumulation in Parkinson's disease models.

Javiera Arcos, Felipe Grunenwald, Denisse Sepulveda, Carolina Jerez, Valentina Urbina, Tomas Huerta, Paulina Troncoso-Escudero, Daniel Tirado, Angela Perez, Rodrigo Diaz-Espinoza and 10 more

Open access · goldAbstract read
In one paragraph

Article in Cell death discovery, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.

  1. Pooled it
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 7 institutions in 3 countries.

Javiera ArcosCenter for Integrative Biology, Universidad Mayor, Santiago, Chile.
Felipe GrunenwaldCenter for Integrative Biology, Universidad Mayor, Santiago, Chile.
Denisse SepulvedaCenter for Integrative Biology, Universidad Mayor, Santiago, Chile.
Carolina JerezCenter for Integrative Biology, Universidad Mayor, Santiago, Chile.
Valentina UrbinaCenter for Integrative Biology, Universidad Mayor, Santiago, Chile.
Tomas HuertaCenter for Integrative Biology, Universidad Mayor, Santiago, Chile.
Paulina Troncoso-EscuderoCenter for Integrative Biology, Universidad Mayor, Santiago, Chile.
Daniel TiradoCenter for Integrative Biology, Universidad Mayor, Santiago, Chile.
Angela PerezCenter for Integrative Biology, Universidad Mayor, Santiago, Chile.
Rodrigo Diaz-EspinozaDepartamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile.
Esteban NovaDepartamento de Química, Facultad de Ciencias Naturales, Matemáticas y Medio Ambiente, Universidad Tecnológica Metropolitana, Santiago, Chile.
Ulrich KubitscheckClausius Institute of Physical and Theoretical Chemistry, University of Bonn, Bonn, Germany.
Juan Eduardo Rodriguez-GaticaClausius Institute of Physical and Theoretical Chemistry, University of Bonn, Bonn, Germany.ORCID http://orcid.org/0000-0003-4123-0104
Claudio HetzBiomedical Neuroscience Institute, University of Chile, Santiago, Chile.
Jorge ToledoBiomedical Neuroscience Institute, University of Chile, Santiago, Chile.
Pablo AhumadaCenter for Integrative Biology, Universidad Mayor, Santiago, Chile.
Diego Rojas-RiveraEscuela de Tecnología Médica, Universidad Mayor, Santiago, Chile.
Elisa Martín-MontañezDepartment of Pharmacology, Faculty of Medicine, Biomedical Research Institute of Malaga, University of Malaga, Malaga, Spain.
María Garcia-FernandezDepartment of Human Physiology, Faculty of Medicine, Biomedical Research Institute of Malaga, University of Malaga, Malaga, Spain.
René L VidalCenter for Integrative Biology, Universidad Mayor, Santiago, Chile. rene.vidal@umayor.cl.ORCID http://orcid.org/0000-0002-4305-7387
Universidad Mayor · CLUniversidad de Málaga · ESUniversity of Bonn · DECenter for Climate and Resilience Research · CLMetropolitan University of Technology · CLUniversidad de Santiago de Chile · CLUniversity of Chile · CL

Funding

Fondo Nacional de Desarrollo Científico y Tecnológico (National Fund for Scientific and Technological Development) 1191003
6 · The paper itself

Abstract

Parkinson's disease (PD) is the second most common late-onset neurodegenerative disease and the predominant cause of movement problems. PD is characterized by motor control impairment by extensive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). This selective dopaminergic neuronal loss is in part triggered by intracellular protein inclusions called Lewy bodies, which are composed mainly of misfolded alpha-synuclein (α-syn) protein. We previously reported insulin-like growth factor 2 (IGF2) as a key protein downregulated in PD patients. Here we demonstrated that IGF2 treatment or IGF2 overexpression reduced the α-syn aggregates and their toxicity by IGF2 receptor (IGF2R) activation in cellular PD models. Also, we observed IGF2 and its interaction with IGF2R enhance the α-syn secretion. To determine the possible IGF2 neuroprotective effect in vivo we used a gene therapy approach in an idiopathic PD model based on α-syn preformed fibrils intracerebral injection. IGF2 gene therapy revealed a significantly preventing of motor impairment in idiopathic PD model. Moreover, IGF2 expression prevents dopaminergic neuronal loss in the SN together with a decrease in α-syn accumulation (phospho-α-syn levels) in the striatum and SN brain region. Furthermore, the IGF2 neuroprotective effect was associated with the prevention of synaptic spines loss in dopaminergic neurons in vivo. The possible mechanism of IGF2 in cell survival effect could be associated with the decrease of the intracellular accumulation of α-syn and the improvement of dopaminergic synaptic function. Our results identify to IGF2 as a relevant factor for the prevention of α-syn toxicity in both in vitro and preclinical PD models.

Identifiers

PMID38042807
PMCPMC10693583
OpenAlexW4389264137

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.