Neurodegenerative disorders have become a serious healthcare problem worldwide and there is no efficacious cure. However, regulating the fate of stem cells is an effective way to treat these neurological diseases. In previous work,
stemazole was reported to maintain the survival of human neural stem cells in the absence of
growth factors and to have
therapeutic effects on
neurodegenerative diseases. However, although it is a promising small molecule, the molecular mechanisms against apoptosis are ambiguous. In this study, tandem mass tag (TMT)-based proteomics were performed to obtain whole
protein expression profiles of human neural stem cells in different groups under extreme conditions. Bioinformatics analysis based on
protein-
protein interaction (PPI) network construction, gene ontology (GO) and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis were adopted to explore crucial
proteins and possible pharmacological mechanisms. A total of 77 differentially expressed
proteins were identified, comprising 38 upregulated
proteins and 39 downregulated
proteins. Combined with a diseases database of
Alzheimer's disease (AD),
caspase-2 (CASP2), PKA C-alpha (PRKACA),
fibronectin (FN1), large neutral
amino acid transporter small subunit 1 (
SLC7A5), which are involved in cell proliferation and apoptosis, this was further validated by
enzyme activity assay and molecular docking, and regarded as putative targets regulated by
stemazole. The present results give an insight into this small molecule and a better understanding for further elucidating the underlying mechanisms in the treatment of stem cells and
neurodegenerative diseases.