Combination of Melatonin and Small Molecules Improved Reprogramming Neural Cell Fates via Autophagy Activation
1
Issued Date
2022-09-01
Resource Type
ISSN
03643190
eISSN
15736903
Scopus ID
2-s2.0-85137958173
Pubmed ID
34165669
Journal Title
Neurochemical Research
Volume
47
Issue
9
Start Page
2580
End Page
2590
Rights Holder(s)
SCOPUS
Bibliographic Citation
Neurochemical Research Vol.47 No.9 (2022) , 2580-2590
Suggested Citation
Sotthibundhu A. Combination of Melatonin and Small Molecules Improved Reprogramming Neural Cell Fates via Autophagy Activation. Neurochemical Research Vol.47 No.9 (2022) , 2580-2590. 2590. doi:10.1007/s11064-021-03382-2 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/83623
Title
Combination of Melatonin and Small Molecules Improved Reprogramming Neural Cell Fates via Autophagy Activation
Author(s)
Other Contributor(s)
Abstract
Reprogramming cell fates towards mature cell types are a promising cell supply for treating degenerative diseases. Recently, transcription factors and some small molecules have turned into impressive modulating elements for reprogramming cell fates. Melatonin, a pineal hormone, has neuroprotective functions including neural stem cell (NSC) proliferative and differentiative modulation in both embryonic and adult brain. We developed a protocol that could be implemented in the direct reprogramming of human skin fibroblast towards neural cells by using histone deacetylase (HDAC) inhibitor, glycogen synthase kinase-3 (GSK3) inhibitor (CHIR99021), c-Jun N-terminal kinase (JNK) inhibitor, rho-associated protein kinase inhibitor (Y-27632), cAMP activator, and melatonin treatment. We found that melatonin enhanced neural-transcription factor genes expressions, including brain-specific homeobox/POU domain protein 2 (BRN2), Achaete-Scute Family BHLH transcription Factor 1 (ASCL1), and Myelin Transcription Factor 1 Like (MYT1L). Melatonin also increased the expression of different neural-specific proteins such as doublecortin (DCX), Sex determining region Y-box 2 (Sox2), and neuronal nuclei (NeuN) compared with other five small molecules (valproic acid (VPA), CHIR99021, Forskolin, 1,9 pyrazoloanthrone (SP600125), and Y-27632) combination in the presence and absence of melatonin. A noticeable upregulation of autophagy proteins (microtubule-associated protein 1A/1B-light chain 3 (LC3) and Beclin-1) were seen in the melatonin treatment during the induction period while these were reverted in the presence of L-leucine, an autophagy inhibitor. In addition, the expression of NeuN was also significantly reduced by L-leucine. Collectively, our findings revealed an activation of autophagy during neural induction; melatonin enhanced reprogramming efficiency for neuron induction through the modulation of autophagy activation.