SH-SY5Y Cell Line In Vitro Models for Parkinson Disease Research—Old Practice for New Trends

Abstract

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.

Both Enantiomers of 2-Hydroxyglutarate Modulate the Metabolism of Cultured Human Neuroblastoma Cells

“…The neuroblastoma cells SH-SY5Y are commonly applied model to study the cytotoxic effects of compounds on human neurons and molecular mechanisms underlying the neurodegeneration [32][33][34][35].…”

In vitro methods in autophagy research: Applications in neurodegenerative diseases and mood disorders

“…It damages dopaminergic neurons and causes aggregation of α-synuclein and Lewy body inclusions ( Salari and Bagheri, 2019 ). Rotenone promotes cell death through the induction of mitochondrial dysfunction, increases oxidative stress, aggregation of α-synuclein, post-translational modifications, and accumulation of autophagy vacuoles leading to neuronal death ( Mader et al, 2012 ; Ioghen et al, 2023 ). Paraquat ( Alvarez-Erviti et al, 2013 ; Baeken et al, 2021 ) is a herbicide that affects the mitochondria causing increased oxidative stress that leads to cellular damage and eventually death of dopaminergic neurons ( Salari and Bagheri, 2019 ).…”

“…The compound 1-methyl-4-phenylpyridinium (MPP+), a metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a gold standard inducer of PD in research settings, that selectively damages dopaminergic neurons, exhibits high affinity to the dopamine transporter leading to its accumulation inside the cells ( Salari and Bagheri, 2019 ; Ioghen et al, 2023 ). MPP+ disrupts the mitochondrial electron transport chain increasing oxidative stress and causing cell damage and neuronal death ( Ioghen et al, 2023 ). The antibiotic bafilomycin A1 (BafA1) is used as an autophagy inhibitor ( Baeken et al, 2021 ; Stathakos et al, 2021 ).…”

Low‐intensity pulsed ultrasound induces proliferation of human neural stem cells

“…22,23 In this context, the human-derived SH-SY5Y neuroblastoma cell line 24 is a basic and consistent neural model for neurological testing. [25][26][27] SH-SY5Y is a subcloned cell line derived from a neuroblastoma of bone marrow in a 4-yearold girl, 24,28 which is widely used in neuroscience such as investigating Parkinson and Alzheimer's diseases, 29,30 neurotoxicity, 31,32 energetic neural vulnerability 33 and being a control model for neurogenic induction of stem cells 34,35 and their neurotrophic effects. 36,37 However, the SH-SY5Y cell cultures lack mature neural features, 33,38,39 and due to neuroblastoma 'cancerous' origin, the cells exhibit high proliferative rate 40 with unsynchronised cell cycles, 22,41 which will negatively affect the reliability and reproducibility of the cell mitosis-related studies such as cell proliferation.…”

“…As it is prohibited to obtain primary human neural stem cells due to ethical concerns, human‐derived neural cell line is an alternative option to study the therapeutic effects 22,23 . In this context, the human‐derived SH‐SY5Y neuroblastoma cell line 24 is a basic and consistent neural model for neurological testing 25–27 . SH‐SY5Y is a subcloned cell line derived from a neuroblastoma of bone marrow in a 4‐year‐old girl, 24,28 which is widely used in neuroscience such as investigating Parkinson and Alzheimer's diseases, 29,30 neurotoxicity, 31,32 energetic neural vulnerability 33 and being a control model for neurogenic induction of stem cells 34,35 and their neurotrophic effects 36,37 .…”