| Literature DB >> 35005630 |
Elisa Navarro1,2,3,4, Evan Udine1,2,3,4, Katia de Paiva Lopes1,2,3,4, Madison Parks1,2,3,4, Giulietta Riboldi5,6, Brian M Schilder1,2,3,4, Jack Humphrey1,2,3,4, Gijsje J L Snijders7,8, Ricardo A Vialle1,2,3,4, Maojuan Zhuang1,2,3,4, Tamjeed Sikder1,2,9,10, Charalambos Argyrou1,2,3,4, Amanda Allan1,2,3,4, Michael J Chao1,2,3,4, Kurt Farrell1,2,9,10, Brooklyn Henderson5, Sarah Simon4,11, Deborah Raymond4,11, Sonya Elango4,11, Roberto A Ortega4,11, Vicki Shanker4,11, Matthew Swan4,11, Carolyn W Zhu12,13,14, Ritesh Ramdhani15, Ruth H Walker4,16, Winona Tse4, Mary Sano12,13,14, Ana C Pereira1,4, Tim Ahfeldt1,2,4, Alison M Goate1,2,3,4, Susan Bressman4,11, John F Crary1,2,9,10, Lotje de Witte7,8, Steven Frucht5, Rachel Saunders-Pullman4,11, Towfique Raj1,2,3,4.
Abstract
An increasing number of identified Parkinson's disease (PD) risk loci contain genes highly expressed in innate immune cells, yet their role in pathology is not understood. We hypothesize that PD susceptibility genes modulate disease risk by influencing gene expression within immune cells. To address this, we have generated transcriptomic profiles of monocytes from 230 individuals with sporadic PD and healthy subjects. We observed a dysregulation of mitochondrial and proteasomal pathways. We also generated transcriptomic profiles of primary microglia from brains of 55 subjects and observed discordant transcriptomic signatures of mitochondrial genes in PD monocytes and microglia. We further identified 17 PD susceptibility genes whose expression, relative to each risk allele, is altered in monocytes. These findings reveal widespread transcriptomic alterations in PD monocytes, with some being distinct from microglia, and facilitate efforts to understand the roles of myeloid cells in PD as well as the development of biomarkers.Entities:
Year: 2021 PMID： 35005630 PMCID： PMC8728893 DOI： 10.1038/s43587-021-00110-x
Source DB: PubMed Journal: Nat Aging ISSN： 2662-8465