| First Author | Endo F | Year | 2015 |
| Journal | Cell Rep | Volume | 11 |
| Issue | 4 | Pages | 592-604 |
| PubMed ID | 25892237 | Mgi Jnum | J:228377 |
| Mgi Id | MGI:5706877 | Doi | 10.1016/j.celrep.2015.03.053 |
| Citation | Endo F, et al. (2015) Astrocyte-derived TGF-beta1 accelerates disease progression in ALS mice by interfering with the neuroprotective functions of microglia and T cells. Cell Rep 11(4):592-604 |
| abstractText | Neuroinflammation, which includes both neuroprotective and neurotoxic reactions by activated glial cells and infiltrated immune cells, is involved in the pathomechanism of amyotrophic lateral sclerosis (ALS). However, the cytokines that regulate the neuroprotective inflammatory response in ALS are not clear. Here, we identify transforming growth factor-beta1 (TGF-beta1), which is upregulated in astrocytes of murine and human ALS, as a negative regulator of neuroprotective inflammatory response. We demonstrate that astrocyte-specific overproduction of TGF-beta1 in SOD1(G93A) mice accelerates disease progression in a non-cell-autonomous manner, with reduced IGF-I production in deactivated microglia and fewer T cells with an IFN-gamma-dominant milieu. Moreover, expression levels of endogenous TGF-beta1 in SOD1(G93A) mice negatively correlate with lifespan. Furthermore, pharmacological administration of a TGF-beta signaling inhibitor after disease onset extends survival time of SOD1(G93A) mice. These findings indicate that astrocytic TGF-beta1 determines disease progression and is critical to the pathomechanism of ALS. |
