Mu opioid receptor-mediated release of endolysosome iron increases levels of mitochondrial iron, reactive oxygen species, and cell death.

Objectives: Opioids including morphine and DAMGO activate mu-opioid receptors (MOR), increase intracellular reactive oxygen species (ROS) levels, and induce cell death. Ferrous iron (Fe) through Fenton-like chemistry increases ROS levels and endolysosomes are "master regulators of iron metabolism" and contain readily-releasable Fe stores. However, mechanisms underlying opioid-induced changes in endolysosome iron homeostasis and downstream-signaling events remain unclear.

The US9-Derived Protein gPTB9TM Modulates APP Processing Without Targeting Secretase Activities.

Alteration of neuronal protein processing is often associated with neurological disorders and is highly dependent on cellular protein trafficking. A prime example is the amyloidogenic processing of amyloid precursor protein (APP) in intracellular vesicles, which plays a key role in age-related cognitive impairment. Most approaches to correct this altered processing aim to limit enzymatic activities that lead to toxic products, such as protein cleavage by β-secretase and the resulting amyloid β production.

Regulation of Tumor and Metastasis Initiation by Chemokine Receptors.

Tumor-initiating cells (TICs) are a rare sub-population of cells within the bulk of a tumor that are major contributors to tumor initiation, metastasis, and chemoresistance. TICs have a stem-cell-like phenotype that is dictated by the expression of master regulator transcription factors, including OCT4, NANOG, and SOX2. These transcription factors are expressed via activation of multiple signaling pathways that drive cancer initiation and progression.