GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE329nnn/GSE329189/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE329189GEOGSEfalsemiR-146a is a pleiotropic regulator of motor neuron degenerationAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons. Here, we have profiled motor neuron microRNAs (miRNAs) during motor neuron degeneration in vivo to gain a better understanding of ALS pathophysiology. We demonstrate that one miRNA, miR-146a, is downregulated in diseased motor neurons despite upregulation in bulk tissue. Genetic deletion of miR-146a significantly extended survival in SOD1G93A mice with heterozygous animals demonstrating the largest benefit. A corresponding reduction in spinal cord gliosis but not motor neuron loss was observed. Finally, we observed that a proportion of miR-146a knockout animals develop spontaneous paralysis, motor neuron loss and chronic neuroinflammation with advanced age. Together these findings demonstrate that a single miRNA influences multiple aspects of motor neuron disease and highlights the complex role for neuroinflammation in ALS pathogenesis.2026/06/01GSE329189GSM9698989GSM9698988GSM9698999GSM9698998GSM9698997GSM9698996GSM9699006GSM9698995GSM9698994GSM9699005GSM9699004GSM9698993GSM9699003GSM9698992GSM9698991GSM9699002GSM9698990GSM9699001GSM969900034328329189Mus musculus