miR-146a is a Pleiotropic Regulator of Motor Neuron Degeneration
Galloway, D. A.; Patterson, H. L.; Hoye, M. L.; Shen, T.; Shabsovich, M.; Schoch, K. M.; Ly, C. V.; Miller, T. M.
Show abstract
Amyotrophic 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.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Purkinje Cell-specific Deficiency in SEL1L-HRD1 Endoplasmic Reticulum-Associated Degradation Causes Progressive Cerebellar Ataxia in Mice 95%
- GABAergic interneurons contribute to the fatal seizure phenotype of CLN2 disease mice 95%
- Benefits of global mutant huntingtin lowering diminish over time in a Huntington's disease mouse model 94%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Antisense therapy in a new rat model of Alexander disease reverses GFAP pathology, white matter deficits, and motor impairment. 96%
- Loss of TDP-43 function and rimmed vacuoles persist after T cell depletion in a xenograft model of sporadic inclusion body myositis 95%
- Transient receptor potential canonical 5 (TRPC5) mediates inflammatory mechanical pain 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.