Life Sciences Commons^™

The Role Of The Circadian Clock Protein Rev-Erba In Neuroinflammation & Synaptic Health, Percy Griffin

Arts & Sciences Electronic Theses and Dissertations

Circadian rhythms are cycles of physiological activity that are conserved across all of life’s taxa – ranging from cyanobacteria to humans - due to their importance. They are conserved to allow organisms to maximize their capacity to obtain resources in their environment. In mammals, light and dark input into the retina is the strongest synchronizer of circadian rhythms. On the molecular level, this tightly regulated transcriptional-translational feedback loop is orchestrated by proteins with cyclical expression. The loss of these proteins has functional consequences on human health and diseases.

Recently, associations have been made between circadian proteins and a host of …

Regulation And Function Of Trem2-Dependent Pathways In Neurodegeneration, Wilbur Madison Song

Arts & Sciences Electronic Theses and Dissertations

Carriers of the R47H allele of the microglia-specific lipid receptor TREM2 have a greatly increased risk of developing Alzheimerճ disease. The objective of this dissertation is to develop further mechanistic knowledge about how TREM2 is regulated and how TREM2 mutations affect microglia and neurodegeneration. Using an in vitro reporter assay, we find that several AD risk-associated TREM2 mutations decrease ligand-dependent activation. Using humanized TREM2 mice, we find that in vivo, the R47H mutation leads to reduced microglia activation and response to A_, as well as decreased shedding of soluble TREM2. These results suggest that TREM2 is protective during disease. We …