IMR Press / JIN / Volume 22 / Issue 1 / DOI: 10.31083/j.jin2201020
Open Access Review
SH-SY5Y Cell Line In Vitro Models for Parkinson Disease Research—Old Practice for New Trends
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1 Cell Biology, Neurosciences and Experimental Myology Laboratory, Victor Babeș Institute of Pathology, 050096 Bucharest, Romania
2 Department of Clinical Neurosciences, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
3 Department of Cellular and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania
*Correspondence: (Laura Cristina Ceafalan)
Academic Editor: Gernot Riedel
J. Integr. Neurosci. 2023, 22(1), 20;
Submitted: 18 August 2022 | Revised: 18 October 2022 | Accepted: 19 October 2022 | Published: 16 January 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

The SH-SY5Y cell line is a simple and inexpensive in vitro experimental model for studying Parkinson disease (PD). This experimental model is a useful tool for elucidating pathophysiological mechanisms of PD and in the development of new pharmacological therapies. In this review, we aim to summarize current protocols for SH-SY5Y cell culturing and differentiation and PD experimental designs derived from the SH-SY5Y cell line. The most efficient protocol for differentiation of the SH-SY5Y cell line into dopaminergic neurons seems to be the addition of retinoic acid to the growth medium, followed by 12-O-tetradecanoylphorbol-13-acetate (TPA) addition in a low concentration of fetal bovine serum. PD pathological changes, such as neuronal apoptosis and the intraneuronal alpha-synuclein aggregation, can be reproduced in the SH-SY5Y cell line either by the use of neurotoxic agents [such as rotenone, 1-methyl-4-phenylpyridinium (MPP+), 6-hydroxydopamine] or by genetic modification (transfection of the alpha-synuclein wild-type or mutant gene, genetic manipulation of other genes involved in PD). In addition, compounds with a potential neuroprotective role may be tested on neurotoxicity-induced SH-SY5Y models. The cell line can also be used for testing PD pathophysiological mechanisms such as the prion-like neuronal transmission of alpha-synuclein or the microbiota influence in PD. In conclusion, the use of the SH-SY5Y cell line represents a basic but consistent first step in experiments related to PD, but which must be followed by the confirmation of the results through more complex in vitro and in vivo experimental models.

SH-SY5Y cell line
Parkinson disease
in vitro model
therapeutic compounds
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31PFE/30.12.2021/Ministry of Research, Innovation and Digitalization in Romania
1N/2019/PN19.29.02.01/National Program
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