Alzheimer's disease (AD) is a chronic degenerative brain disorder with no clear pathogenesis or effective cure, accounting for 60-80% of cases of dementia. In recent years, the importance of neuroinflammation in the pathogenesis of AD and other neurodegenerative disorders has come into focus. Previously, we made the serendipitous discovery that the widely used drug excipient N,N-dimethylacetamide (DMA) attenuates endotoxin-induced inflammatory responses in vivo.
View Article and Find Full Text PDFGrowth and differentiation factor 8 (GDF8) is a TGF-β superfamily member, and negative regulator of skeletal muscle mass. GDF8 inhibition results in prominent muscle growth in mice, but less impressive hypertrophy in primates, including man. Broad TGF-β inhibition suggests another family member negatively regulates muscle mass, and its blockade enhances muscle growth seen with GDF8-specific inhibition.
View Article and Find Full Text PDFBackground: Higher-than-normal levels of circulating triglycerides are a risk factor for ischemic cardiovascular disease. Activation of lipoprotein lipase, an enzyme that is inhibited by angiopoietin-like 4 (ANGPTL4), has been shown to reduce levels of circulating triglycerides.
Methods: We sequenced the exons of ANGPTL4 in samples obtain from 42,930 participants of predominantly European ancestry in the DiscovEHR human genetics study.
Data suggest both presynaptic and postsynaptic changes contribute to activity-dependent long-term synaptic plasticity. We have shown that pairing elevation of intracellular [cyclic GMP], using the type V phosphodiesterase inhibitor zaprinast, with inhibition of cyclic AMP-dependent protein kinase (PKA), is sufficient to elicit chemical long-term depression (CLTD) of synaptic transmission at Schaffer collateral-CA1 and mossy fibre-CA3 synapses in rat hippocampus. CLTD does not require synaptic activity, and selective postsynaptic drug injections do not affect it, suggesting it is presynaptically induced and expressed.
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