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Rapid induction of dopaminergic neuron-like cells from human fibroblasts by autophagy activation with only 2-small molecules

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Abstract

The dopaminergic neurons are responsible for the release of dopamine. Several diseases that affect motor function, including Parkinson's disease (PD), are rooted in inadequate dopamine (DA) neurotransmission. The study's goal was to create a quick way to make dopaminergic neuron-like cells from human fibroblasts (hNF) using only two small molecules: hedgehog pathway inhibitor 1 (HPI-1) and neurodazine (NZ). Two small compounds have been shown to induce the transdifferentiation of hNF cells into dopaminergic neuron-like cells. After 10 days of treatment, hNF cells had a big drop in fibroblastic markers (Col1A1, KRT18, and Elastin) and a rise in neuron marker genes (TUJ1, PAX6, and SOX1). Different proteins and factors related to dopaminergic neurons (TH, TUJ1, and dopamine) were significantly increased in cells that behave like dopaminergic neurons after treatment. A study of the autophagy signaling pathway showed that apoptotic genes were downregulated while autophagy genes (LC3, ATG5, and ATG12) were significantly upregulated. Our results showed that treating hNF cells with both HPI-1 and NZ together can quickly change them into mature neurons that have dopaminergic activity. However, the current understanding of the underlying mechanisms involved in nerve guidance remains unstable and complex. Ongoing research in this field must continue to advance for a more in-depth understanding. This is crucial for the safe and highly effective clinical application of the knowledge gained to promote neural regeneration in different neurological diseases.

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Data availability

The data analyzed in this study are available from the corresponding author on reasonable request.

Abbreviations

PD:

Parkinson's disease

DA:

dopamine

TH:

tyrosine hydroxylase

hNF:

human fibroblasts

HPI-1:

hedgehog pathway inhibitor 1

NZ:

neurodazine

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Acknowledgements

This work was supported by the Suranaree University of Technology (SUT) Research and Development Fund, Thailand Science Research and Innovation (TSRI), National Science, Research and Innovation Fund (NSRF) (project code 90464), and the NSRF via the Program Management Unit for Human Resources & Institutional Development, Research, and Innovation (PMU-B) (grant number B13F660133).

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Authors and Affiliations

  1. Laboratory of Cell-Based Assays and Innovations, School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, 111 University Avenue, Nakhon Ratchasima, 30000, Thailand

    Natchadaporn Sorraksa, Palakorn Kaokaen, Phongsakorn Kunhorm, Nudjanad Heebkaew, Wilasinee Promjantuek & Parinya Noisa

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  1. Natchadaporn Sorraksa
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  2. Palakorn Kaokaen
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Correspondence to Parinya Noisa.

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Sorraksa, N., Kaokaen, P., Kunhorm, P. et al. Rapid induction of dopaminergic neuron-like cells from human fibroblasts by autophagy activation with only 2-small molecules. 3 Biotech 14, 115 (2024). https://doi.org/10.1007/s13205-024-03957-0

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