Medical Physiology Commons^™

Myeloid Arginase 1 Insufficiency Exacerbates Amyloid-Β Associated Neurodegenerative Pathways And Glial Signatures In A Mouse Model Of Alzheimer’S Disease: A Targeted Transcriptome Analysis, Chao Ma, Jerry B. Hunt, Andrii Kovalenko, Huimin Liang, Maj-Linda B. Selenica, Michael B. Orr, Bei Zhang, John C. Gensel, David J. Feola, Marcia N. Gordon, Dave Morgan, Paula C. Bickford, Daniel C. Lee

Sanders-Brown Center on Aging Faculty Publications

Brain myeloid cells, include infiltrating macrophages and resident microglia, play an essential role in responding to and inducing neurodegenerative diseases, such as Alzheimer’s disease (AD). Genome-wide association studies (GWAS) implicate many AD casual and risk genes enriched in brain myeloid cells. Coordinated arginine metabolism through arginase 1 (Arg1) is critical for brain myeloid cells to perform biological functions, whereas dysregulated arginine metabolism disrupts them. Altered arginine metabolism is proposed as a new biomarker pathway for AD. We previously reported Arg1 deficiency in myeloid biased cells using lysozyme M (LysM) promoter-driven deletion worsened amyloidosis-related neuropathology and behavioral impairment. However, …

CertL Reduces C16 Ceramide, Amyloid-Β Levels, And Inflammation In A Model Of Alzheimer’S Disease, Simone M. Crivelli, Qian Luo, Jo A. A. Stevens, Caterina Giovagnoni, Daan Van Kruining, Gerard Bode, Sandra Den Hoedt, Barbara Hobo, Anna-Lena Scheithauer, Jochen Walter, Monique T. Mulder, Christopher Exley, Matthew Mold, Michelle M. Mielke, Helga E. De Vries, Kristiaan Wouters, Daniel L. A. Van Den Hove, Dusan Berkes, María Dolores Ledesma, Joost Verhaagen, Mario Losen, Erhard Bieberich, Pilar Martinez-Martinez

Physiology Faculty Publications

BACKGROUND: Dysregulation of ceramide and sphingomyelin levels have been suggested to contribute to the pathogenesis of Alzheimer's disease (AD). Ceramide transfer proteins (CERTs) are ceramide carriers which are crucial for ceramide and sphingomyelin balance in cells. Extracellular forms of CERTs co-localize with amyloid-β (Aβ) plaques in AD brains. To date, the significance of these observations for the pathophysiology of AD remains uncertain.

METHODS: A plasmid expressing CERT_L, the long isoform of CERTs, was used to study the interaction of CERT_L with amyloid precursor protein (APP) by co-immunoprecipitation and immunofluorescence in HEK cells. The recombinant CERT_L protein …