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Cited by 18Parkinson's Disease Mechanisms and TreatmentsPluripotent Stem Cells ResearchNuclear Receptors and Signaling

Dissecting the non-neuronal cell contribution to Parkinson’s disease pathogenesis using induced pluripotent stem cells

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Pons-Espinal, Meritxell, Blasco-Agell, Lucas, Consiglio, Antonella·2021·Cellular and Molecular Life Sciences
DOI 10.1007/s00018-020-03700-xPMC PMC7966189
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Abstract

Parkinson’s disease (PD) is an incurable age-linked neurodegenerative disease with characteristic movement impairments that are caused by the progressive loss of dopamine-containing neurons (DAn) within the substantia nigra pars compacta. It has been suggested that misfolded protein aggregates together with neuroinflammation and glial reactivity, may impact nerve cell function, leading to neurodegeneration and diseases, such as PD. However, not many studies have been able to examine the role of human glial cells in the pathogenesis of PD. With the advent of induced pluripotent stem cell (iPSC) technology, it is now possible to reprogram human somatic cells to pluripotency and to generate viable human patient-specific DA neurons and glial cells, providing a tremendous opportunity for dissecting cellular and molecular pathological mechanisms occurring at early stages of PD. This reviews will report on recent work using human iPSC and 3D brain organoid models showing that iPSC technology can be used to recapitulate PD-relevant disease-associated phenotypes, including protein aggregation, cell death or loss of neurite complexity and deficient autophagic vacuoles clearance and focus on the recent co-culture systems that are revealing new insights into the complex interactions that occur between different brain cell types during neurodegeneration. Consequently, such advances are the key to improve our understanding of PD pathology and generate potential targets for new therapies aimed at curing PD patients.

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Authors
Pons-Espinal, M., Blasco-Agell, L., & Consiglio, A.
Affiliations
Bellvitge University Hospital (ES)
Corresponding author
Consiglio, Antonella
ORCID
Venue
Cellular and Molecular Life Sciences
Publisher
Springer Science and Business Media LLC
Published
2020-11-18
Volume
78
Issue
5
Pages
2081-2094
ISSN
  • 1420-682X (ISSN-L)
  • 1420-9071
DOI
10.1007/s00018-020-03700-x
PMC
PMC7966189
OpenAlex
W3105115899
Cited by
18
References
29
Citations by year
2026: 4 · 2025: 3 · 2024: 1 · 2023: 5 · 2022: 4 · 2021: 1
FWCI
0.28
Type
journal article
Language
en
Open access
Licence
Locations
  • Cellular and Molecular Life Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, cc-by)
  • Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
Funders
  • European Research Council (2012-StG-311736)
  • Ministerio de Economía y Competitividad (BFU2016-80870-P, BES-2017-080579)
  • Instituto de Salud Carlos III (RD16/0011/0024)
  • Generalitat de Catalunya (AGAUR (2017-SGR-899), 2017 BP 00133)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
Keywords
Parkinson's disease, induced pluripotent stem cells, glial cells, dopaminergic neurons, substantia nigra pars compacta, neuroinflammation, protein aggregation, autophagy, brain organoids, co-culture model, neurodegeneration, disease modeling, therapeutic target
MeSH terms
Animals, Astrocytes, Humans, Neuroglia, Organoids, Parkinson Disease, Substantia Nigra, Cell Culture Techniques, Induced Pluripotent Stem Cells, Dopaminergic Neurons

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