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Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder that is characterized by a progressive degeneration of motor neurons (MNs). The pathomechanism underlying the disease is largely unknown, even though increasing evidence suggests that RNA metabolism, including microRNAs (miRNAs) may play an important role. In this study, human ALS induced pluripotent stem cells were differentiated into MN progenitors and their miRNA expression profiles were compared to those of healthy control cells. We identified 15 downregulated miRNAs in patients’ cells. Gene ontology and molecular pathway enrichment analysis indicated that the predicted target genes of the differentially expressed miRNAs were involved in neurodegeneration-related pathways. Among the 15 examined miRNAs, miR-34a and miR504 appeared particularly relevant due to their involvement in the p53 pathway, synaptic vesicle regulation and general involvement in neurodegenerative diseases. Taken together our results demonstrate that the neurodegenerative phenotype in ALS can be associated with a dysregulation of miRNAs involved in the control of disease-relevant genetic pathways, suggesting that targeting entire gene networks can be a potential strategy to treat complex diseases such as ALS.

MicroRNA expression analysis identifies a subset of downregulated miRNAs in ALS motor neuron progenitors