Recapitulating Parkinson's disease pathology in a three-dimensional human neural cell culture model.

TAYLOR-WHITELEY, Teresa R, LE MAITRE, Christine L, DUCE, James A, DALTON, Caroline F and SMITH, David P (2019). Recapitulating Parkinson's disease pathology in a three-dimensional human neural cell culture model. Disease Models & Mechanisms, 12 (4).

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Official URL: http://dmm.biologists.org/content/12/4/dmm038042
Open Access URL: http://dmm.biologists.org/content/dmm/12/4/dmm0380... (Published version)
Link to published version:: https://doi.org/10.1242/dmm.038042
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    Abstract

    Extensive loss of dopaminergic neurons, and aggregation of the protein α-synuclein into ubiquitin-positive Lewy bodies represents a major neuropathological hallmark of Parkinson's disease. At present the generation of large nuclear-associated Lewy bodies from endogenous wild-type α-synuclein, translationally regulated under its own promoter in human cell culture models requires costly and time-consuming protocols. Here, we demonstrate that fully differentiated human SH-SY5Y neuroblastoma cells grown in three-dimensional cell culture develop Lewy body-like pathology upon exposure to exogenous α-synuclein species. In contrast to most cell- and rodent-based models that exhibit multiple diffuse α-synuclein aggregates throughout the cytoplasm, a single large nuclear inclusion immuno-positive for α-synuclein and ubiquitin is rapidly obtained in our model. This was achieved, without the need for over-expression of α-synuclein or genetic modification of the cell line. However, phosphorylation of α-synuclein within these inclusions was not observed. The system described here provides an ideal tool to screen compounds to therapeutically intervene in Lewy body formation and to investigate the mechanisms involved in disease progression in synucleinopathies.

    Item Type: Article
    Uncontrolled Keywords: 3D Cell Culture; Amyloid; Lewy Body; Oligomer; Parkinsons; Synuclein; Developmental Biology; 06 Biological Sciences; 11 Medical and Health Sciences
    Identification Number: https://doi.org/10.1242/dmm.038042
    SWORD Depositor: Symplectic Elements
    Depositing User: Symplectic Elements
    Date Deposited: 09 Apr 2019 11:40
    Last Modified: 17 Apr 2019 09:30
    URI: http://shura.shu.ac.uk/id/eprint/24381

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