Agouti Related Peptide Secreted Via Human Mesenchymal Stem Cells Upregulates Proteasome Activity in an Alzheimer's Disease Model

作者：Lee Na Kyung; Park Sang Eon; Kwon Soo Jin; Shim Sangmi; Byeon Yeji; Kim Jong Hwa; Na Duk L^*; Chang Jong Wook^*

来源：Scientific Reports, 2017, 7(1): 39340.

DOI：10.1038/srep39340

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.

• 出版日期2017-1-4