| First Author | Parisi C | Year | 2016 |
| Journal | Cell Death Differ | Volume | 23 |
| Issue | 3 | Pages | 531-41 |
| PubMed ID | 26794445 | Mgi Jnum | J:261726 |
| Mgi Id | MGI:6141509 | Doi | 10.1038/cdd.2015.153 |
| Citation | Parisi C, et al. (2016) MicroRNA-125b regulates microglia activation and motor neuron death in ALS. Cell Death Differ 23(3):531-41 |
| abstractText | Understanding the means by which microglia self-regulate the neuroinflammatory response helps modulating their reaction during neurodegeneration. In amyotrophic lateral sclerosis (ALS), classical NF-kappaB pathway is related to persistent microglia activation and motor neuron injury; however, mechanisms of negative control of NF-kappaB activity remain unexplored. One of the major players in the termination of classical NF-kappaB pathway is the ubiquitin-editing enzyme A20, which has recognized anti-inflammatory functions. Lately, microRNAs are emerging as potent fine-tuners of neuroinflammation and reported to be regulated in ALS, for instance, by purinergic P2X7 receptor activation. In this work, we uncover an interplay between miR-125b and A20 protein in the modulation of classical NF-kappaB signaling in microglia. In particular, we establish the existence of a pathological circuit in which termination of A20 function by miR-125b strengthens and prolongs the noxious P2X7 receptor-dependent activation of NF-kappaB in microglia, with deleterious consequences on motor neurons. We prove that, by restoring A20 levels, miR-125b inhibition then sustains motor neuron survival. These results introduce miR-125b as a key mediator of microglia dynamics in ALS. |
