Myotubularin-related protein protects against neuronal degeneration mediated by oxidative stress or infection

Microbial infections have been linked to the onset and severity of neurodegenerative diseases such as amyotrophic lateral sclerosis, multiple sclerosis, Alzheimer's disease, but the underlying mechanisms remain largely unknown. Here, we used a genetic screen for genes involved in protection from infection-associated neurodegeneration and identified the gene mtm-10. We then validated the role of the encoded myotubularin-related protein, MTM-10, in protecting the dendrites of Caenorhabditis elegans from degeneration mediated by oxidative stress or Pseudomonas aeruginosa infection. Further experiments indicated that mtm-10 is expressed in the AWC neurons of C. elegans, where it functions in a cell autonomous manner to protect the dendrite degeneration caused by pathogen infection. We also confirm that the changes observed in the dendrites of the animals were not because of premature death or overall sickness. Finally, our studies indicated that mtm-10 functions in AWC neurons to preserve chemosensation after pathogen infection. These results reveal an essential role for myotubularin-related protein 10 in the protection of dendrite morphology and function against the deleterious effects of oxidative stress or infection.

Automated summary

The gene mtm-10, which encodes the myotubularin-related protein MTM-10, has been identified as playing an essential role in protecting dendrite morphology and function against the harmful effects of oxidative stress or infection. MTM-10 is expressed in the AWC neurons of Caenorhabditis elegans and functions in a cell autonomous manner to prevent dendrite degeneration caused by pathogen infection. This study reveals a novel mechanism underlying the link between microbial infections and neurodegenerative diseases.