title: Agouti Related Peptide Secreted Via Human Mesenchymal Stem Cells Upregulates Proteasome Activity in an Alzheimer's Disease Model.
abstract: 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.
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.|Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea.|Stem Cell &Regenerative Medicine Institute, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Na Kyung
authors.initials: NK
authors.lastname: Lee
authors.affiliation: Stem Cell &Regenerative Medicine Institute, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Sang Eon
authors.initials: SE
authors.lastname: Park
authors.affiliation: Stem Cell &Regenerative Medicine Institute, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Kwon
authors.affiliation: Department of Biomedical Sciences, Seoul National University, Seoul, Republic of Korea.
authors.forename: Sangmi
authors.initials: S
authors.lastname: Shim
authors.affiliation: Stem Cell &Regenerative Medicine Institute, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Yeji
authors.initials: Y
authors.lastname: Byeon
authors.affiliation: Department of Obstetrics and Gynecology, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Jong-Hwa
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.|Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.|Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea.|Stem Cell &Regenerative Medicine Institute, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Duk L
authors.initials: DL
authors.lastname: Na
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.|Stem Cell &Regenerative Medicine Institute, Samsung Medical Center, Seoul, Republic of Korea.
authors.forename: Jong Wook
authors.initials: JW
authors.lastname: Chang
mesh_terms: D054369:Agouti-Related Protein / Q000378:metabolism*; D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D001691:Biological Therapy; D002460:Cell Line; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D004195:Disease Models, Animal; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: C515198:AGRP protein, human; D054369:Agouti-Related Protein; D017077:Culture Media, Conditioned; D046988:Proteasome Endopeptidase Complex