SH-SY5Y is a human neuroblastoma cell line widely used as an in vitro model for studying neurodegenerative diseases, particularly Parkinson's disease (PD), Alzheimer's disease (AD), and related disorders. This cell line serves as a valuable tool for investigating neuronal differentiation, synaptic function, neurotoxicity, and therapeutic drug screening.
SH-SY5Y is a subclone of the SK-N-SH cell line, which was originally established in 1970 from a metastatic bone tumor of a 4-year-old female patient with neuroblastoma[1]. The SK-N-SH line was subsequently cloned to generate the SH-SY5Y subclone, which exhibits enhanced neuronal differentiation potential compared to the parent line[2].
| Property | Value |
|---|---|
| Species | Human (Homo sapiens) |
| Tissue | Bone marrow (metastatic neuroblastoma) |
| Age | 4 years old (donor) |
| Sex | Female |
| Karyotype | Modal number = 47 (trisomy 1q) |
| Blood type | A, Rh+ |
| Growth pattern | Mixed adherent/suspension |
| Population doubling time | ~48 hours |
| ATCC Catalog | CRL-2266 |
In their undifferentiated state, SH-SY5Y cells exhibit a neuroblast-like morphology with both adherent and non-adherent populations. They express low levels of neuronal markers and retain some characteristics of proliferative neural crest-derived cells. Key features include:
Upon treatment with differentiation agents, SH-SY5Y cells undergo morphological and biochemical changes resembling mature neurons:
Retinoic acid is the most commonly used differentiation agent for SH-SY5Y cells. RA activates nuclear retinoic acid receptors (RARs), which regulate gene expression programs involved in neuronal maturation[3].
Protocol Overview:
Molecular Mechanisms:
Brain-derived neurotrophic factor (BDNF) promotes neuronal survival and differentiation through TrkB receptor activation[4]. BDNF treatment following RA priming produces more mature dopaminergic neurons.
Protocol Overview:
| Agent | Concentration | Duration | Outcome |
|---|---|---|---|
| dbcAMP | 1 mM | 5-7 days | Neurite outgrowth |
| GDNF | 20 ng/mL | 7-10 days | Dopaminergic phenotype |
| TPA | 80 nM | 3-5 days | Neuronal morphology |
| DAPT | 10 μM | 5 days | GABAergic differentiation |
SH-SY5Y cells are extensively used as a Parkinson's disease model due to their ability to differentiate into dopaminergic-like neurons. Key research applications include:
SH-SY5Y cells serve as a high-throughput screening platform for potential PD therapeutics:
LRRK2 (leucine-rich repeat kinase 2) is the most common genetic cause of familial PD. SH-SY5Y cells with LRRK2 mutations (G2019S, R1441C/G/H) are used to study:
Beyond PD, SH-SY5Y cells are valuable for AD research:
| Cell Line | Origin | Characteristics |
|---|---|---|
| SK-N-SH | Neuroblastoma (parent line) | Mixed phenotype, less differentiated |
| SK-N-Be(2) | Neuroblastoma | Catecholaminergic |
| PC12 | Rat pheochromocytoma | Rat origin, NGF-differentiable |
| LUHMES | Immortalized human neurons | Highly differentiated, post-mitotic |
| iPSC-derived neurons | Induced pluripotent stem cells | Patient-specific, more physiological |
Biedler et al. [Human Neuroblastoma Cells in Continuous Culture (1978)](https://doi.org/10.1016/0014-5793(78). 1978. ↩︎
Encinas et al. Sequential Treatment of SH-SY5Y Cells with Retinoic Acid and Brain-Derived Neurotrophic Factor (2000). 2000. ↩︎
Kaplan et al. Neurotrophin-induced signaling in SH-SY5Y cells (1991). 1991. ↩︎