Combination of Melatonin and Small Molecules Improved Reprogramming Neural Cell Fates via Autophagy Activation.
In: Neurochemical Research, Jg. 47 (2022-09-01), Heft 9, S. 2580-2590
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Zugriff:
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. [ABSTRACT FROM AUTHOR]
Titel: |
Combination of Melatonin and Small Molecules Improved Reprogramming Neural Cell Fates via Autophagy Activation.
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Autor/in / Beteiligte Person: | Sotthibundhu, Areechun ; Nopparat, Chutikorn ; Natphopsuk, Sitakan ; Phuthong, Sophida ; Noisa, Parinya ; Govitrapong, Piyarat |
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Zeitschrift: | Neurochemical Research, Jg. 47 (2022-09-01), Heft 9, S. 2580-2590 |
Veröffentlichung: | 2022 |
Medientyp: | academicJournal |
ISSN: | 0364-3190 (print) |
DOI: | 10.1007/s11064-021-03382-2 |
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