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The mechanisms of human mutant superoxide dismutase-1 (mSOD1) toxicity to motor neurons (MNs) are unresolved. We show that MNs in G93A-mSOD1 transgenic mice undergo slow degeneration lacking similarity to apoptosis structurally and biochemically. It is characterized by somal and mitochondrial swelling and formation of DNA single-strand breaks prior to(More)
The mechanisms of injury-induced apoptosis of neurons within the spinal cord are not understood. We used a model of peripheral nerve-spinal cord injury in the rat and mouse to induce motor neuron degeneration. In this animal model, unilateral avulsion of the sciatic nerve causes apoptosis of motor neurons. We tested the hypothesis that p53 and Bax regulate(More)
Cerebral cortical neuron degeneration occurs in brain disorders manifesting throughout life, but the mechanisms are understood poorly. We used cultured embryonic mouse cortical neurons and an in vivo mouse model to study mechanisms of DNA damaged-induced apoptosis in immature and differentiated neurons. p53 drives apoptosis of immature and differentiated(More)
Amyotrophic lateral sclerosis is a fatal disease caused by degeneration of motor neurons (MNs). We transplanted multipotent neural precursor cell (NPC)-neurospheres from mouse olfactory bulb (OB) into the spinal cord of transgenic mice that develop MN degeneration because of human mutant superoxide dismutase-1 (mSOD1). Adult NPCs were isolated from the OB(More)
Colorectal cancer is a leading cause of cancer-related deaths. Mutations in the innate immune sensor AIM2 are frequently identified in patients with colorectal cancer, but how AIM2 modulates colonic tumorigenesis is unknown. Here, we found that Aim2-deficient mice were hypersusceptible to colonic tumor development. Production of inflammasome-associated(More)
The mechanisms of injury- and disease-related degeneration of motor neurons (MNs) need clarification. Unilateral avulsion of the sciatic nerve in the mouse induces apoptosis of spinal MNs that is p53 and Bax dependent. We tested the hypothesis that MN apoptosis is Fas death receptor dependent and triggered by nitric oxide (NO)- and superoxide-mediated(More)
The olfactory bulb (OB) core is an extension of the rostral migratory stream and thus is a potential source of neural progenitor and neural stem cells. We characterized in vivo and in vitro neuronal progenitor and neural stem cells in the adult OB core. In mouse and rat, bromodeoxyuridine (BrdU) labeling showed that the OB core accumulates newly replicated(More)
Leptin and its long form receptor, Ob-Rb, in the hypothalamus play a key function in regulating food intake and body weight. We demonstrate here that apolipoprotein D (Apo D), a lipocalin that is heavily expressed in brain, interacts specifically with the cytoplasmic portion of Ob-Rb but not the short form receptor, Ob-Ra. This finding is detected in yeast(More)
Stimulator of IFN genes (STING) is a cytoplasmic innate immune sensor for cyclic dinucleotides that also serves a dual role as an adaptor molecule for a number of intracellular DNA receptors. Although STING has important functions in the host defense against pathogens and autoimmune diseases, its physiological role in cancer is unknown. In this study, we(More)
Enteric pathogens represent a major cause of morbidity and mortality worldwide. Toll-like receptor (TLR) and inflammasome signaling are critical for host responses against these pathogens, but how these pathways are integrated remains unclear. Here, we show that TLR4 and the TLR adaptor TRIF are required for inflammasome activation in macrophages infected(More)