| First Author | Tung YT | Year | 2019 |
| Journal | Cell Stem Cell | Volume | 25 |
| Issue | 2 | Pages | 193-209.e7 |
| PubMed ID | 31155482 | Mgi Jnum | J:283875 |
| Mgi Id | MGI:6390443 | Doi | 10.1016/j.stem.2019.04.016 |
| Citation | Tung YT, et al. (2019) Mir-17 approximately 92 Confers Motor Neuron Subtype Differential Resistance to ALS-Associated Degeneration. Cell Stem Cell 25(2):193-209.e7 |
| abstractText | Progressive degeneration of motor neurons (MNs) is the hallmark of amyotrophic lateral sclerosis (ALS). Limb-innervating lateral motor column MNs (LMC-MNs) seem to be particularly vulnerable and are among the first MNs affected in ALS. Here, we report association of this differential susceptibility with reduced expression of the mir-17 approximately 92 cluster in LMC-MNs prior to disease onset. Reduced mir-17 approximately 92 is accompanied by elevated nuclear PTEN in spinal MNs of presymptomatic SOD1(G93A) mice. Selective dysregulation of the mir-17 approximately 92/nuclear PTEN axis in degenerating SOD1(G93A) LMC-MNs was confirmed in a double-transgenic embryonic stem cell system and recapitulated in human SOD1(+/L144F)-induced pluripotent stem cell (iPSC)-derived MNs. We further show that overexpression of mir-17 approximately 92 significantly rescues human SOD1(+/L144F) MNs, and intrathecal delivery of adeno-associated virus (AAV)9-mir-17 approximately 92 improves motor deficits and survival in SOD1(G93A) mice. Thus, mir-17 approximately 92 may have value as a prognostic marker of MN degeneration and is a candidate therapeutic target in SOD1-linked ALS. VIDEO ABSTRACT. |
