Modulation of GPRC6A Signaling to Mitigate Tauopathies
Poster Feb 15, 2017
Chao Ma, Jerry Hunt, Leslie Sandusky PhD, Ronald Alvarez, William Fraser, Dali Zheng PhD, Siddharth Kamath PhD, Chad Dickey PhD, Hans Bra ̈uner-Osborne PhD, Daniel Sejer Pedersen PhD, Kevin Nash PhD, Dave Morgan PhD, Daniel Lee PhD
Microtubule associated protein named tau, often becomes hyperphosphorylated and aggregates to form pathological neurofibrillary tangles in several age-associated neurodegenerative diseases known as tauopathies. Clinical phenotypes of tauopathies manifest as cognitive impairment, behavior disturbances and motor impairment. The aggregation of tau remains a central target for drug discovery, but currently no disease-modifying treatments exist. Our group has recently uncovered a unique interaction between L-arginine metabolism and tauopathies. We found that the depletion of L-arginine by overexpressing the metabolizing enzyme arginase 1 and arginine deiminase significantly reduced tau pathology in transgenic mouse models. We speculate that these effects associate with increased autophagy through amino acid sensing. G protein-coupled receptor (GPCR), family C, group 6, member A (GPRC6A) was deorphanized by binding to basic L-α amino acids, like L-arginine. We hypothesize that decreased GPRC6A signaling inhibits mTORC1 activation and thus promoting autophagy to induce tau clearance in tauopathies. We posit that GPRC6A remains tonically activated and senses extracellular amino acids sufficiency of L-α amino acids, especially becomes more sensitive to L-arginine in tauopathies.
Depression, Anxiety and Apathy in Young-Onset and Atypical Dementia: A systematic reviewPoster
This study aims to examine the body of empirical studies investigating the prevalence of depression, anxiety, and apathy in atypical and young-onset dementia.
Psychiatric Risk Gene Cacna1c and Early Life Stress: Potential Gene-Environment interactions?Poster
Early life stress (ELS) is highly associated with development of psychopathology
and mood disorders in adulthood. Genetic studies have identified variation in the gene calcium voltage-gated channel subunit alpha1C (CACNA1C) to increase risk for several psychiatric disorders. This poster assessed the expression of Cacna1c following prepubertal stress.
Regulatory T-Cells (Tregs) Within Bone Marrow-Derived Stem Cells (BMSCs) Actively Confer Immunomodulatory and Neuroprotective Effects Against StrokePoster
We found a distinct subpopulation of Tregs within BMSCs. Tregs and BMSCs in co-culture conferred neuroprotection that varied in a dose-dependent manner. Tregs minimized stem cell production of IL-6, a pro-inflammatory cytokine, and inhibited BMSC secretion of FGF-beta, a cytokine related to BMSC proliferation and differentiation. The ratio of Tregs found natively in BMSCs is optimally adapted to provide the maximum neuroprotective benefit of stem cell treatment after ischemic stroke.READ MORE