| First Author | Lee NK | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Pages | 39340 | PubMed ID | 28051110 |
| Mgi Jnum | J:348871 | Mgi Id | MGI:7645587 |
| Doi | 10.1038/srep39340 | Citation | Lee NK, et al. (2017) Agouti Related Peptide Secreted Via Human Mesenchymal Stem Cells Upregulates Proteasome Activity in an Alzheimer's Disease Model. Sci Rep 7:39340 |
| abstractText | The activity of the ubiquitin proteasome system (UPS) is downregulated in aggregation diseases such as Alzheimer's disease (AD). In this study, we investigated the therapeutic potential of the Agouti-related peptide (AgRP), which is secreted by human mesenchymal stem cells (MSCs), in terms of its effect on the regulation of proteasome activity in AD. When SH-SY5Y human neuroblastoma cells were co-cultured with MSCs isolated from human Wharton's Jelly (WJ-MSC), their proteasome activity was significantly upregulated. Further analysis of the conditioned media after co-culture allowed us to identify significant concentrations of a neuropeptide, called AgRP. The stereotactic delivery of either WJ-MSCs or AgRP into the hippocampi of C57BL6/J and 5XFAD mice induced a significant increase of proteasome activity and suppressed the accumulation of ubiquitin-conjugated proteins. Collectively, these findings suggest strong therapeutic potential for WJ-MSCs and AgRP to enhance proteasome activity, thereby potentially reducing abnormal protein aggregation and delaying the clinical progression of various neurodegenerative diseases. |
