A5044269600- Glycosylation and Glycoproteins Research
- Lysosomal Storage Disorders Research
- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- Carbohydrate Chemistry and Synthesis
- Alzheimer's disease research and treatments
- Receptor Mechanisms and Signaling
- Neurological disorders and treatments
- Mitochondrial Function and Pathology
- Prenatal Substance Exposure Effects
- Cholinesterase and Neurodegenerative Diseases
- Memory and Neural Mechanisms
- Neuroscience of respiration and sleep
- Tryptophan and brain disorders
- Nicotinic Acetylcholine Receptors Study
- Genetic Neurodegenerative Diseases
- Birth, Development, and Health
Biogen (United States)
2020
Research & Development Institute
2013
Ono Pharmaceutical (United States)
2013
University of Washington
2004-2009
Seattle Children's Hospital
2006-2008
Normal striatal function is dependent on the availability of synaptic dopamine to modulate neurotransmission. Within striatum, excitatory inputs from cortical glutamatergic neurons and modulatory midbrain converge onto dendritic spines medium spiny neurons. In addition receptors neurons, D2 are also present corticostriatal terminals, where they act dampen excitation. To determine effect depletion activity, we used styryl dye FM1-43 in combination with multiphoton confocal microscopy slice...
Huntington disease is a genetic neurodegenerative disorder that produces motor, neuropsychiatric, and cognitive deficits caused by an abnormal expansion of the CAG tract in huntingtin (htt) gene. In humans, mutated htt induces preferential loss medium spiny neurons striatum and, to lesser extent, cortical as progresses. The mechanisms causing these degenerative changes remain unclear, but they may involve synaptic dysregulation. We examined activity corticostriatal pathway using combination...
Aggregation of tau into paired helical filaments is a pathological process leading to neurotoxicity in Alzheimer's disease and other tauopathies. Tau posttranslationally modified by O-linked N-acetylglucosamine (O-GlcNAc), increasing O-GlcNAcylation may protect against its aggregation. Research tools study the relationship between aggregation have not been widely available. Here we describe generation rabbit monoclonal antibody specific for O-GlcNAcylated at Ser400 (O-tau(S400)). We show...
Hyperphosphorylated tau protein is a pathological hallmark of numerous neurodegenerative diseases and the level pathology correlated with degree cognitive impairment. Tau hyper-phosphorylation thought to be an early initiating event in cascade leading toxicity neuronal death. Inhibition phosphorylation therefore represents attractive therapeutic strategy. However, widespread expression most kinases promiscuity their substrates, along poor selectivity kinase inhibitors, have resulted systemic...
Novel non-carbohydrate O-GlcNAcase inhibitors with CNS drug properties as potential treatment for Alzheimer’s disease and tauopathies Heike Hering, Danielle Graham, Solenne Ousson, Maud Neny, Audrey Gray, Brandy Giacomozzi, John Joyce, Vikram Dutt, Michael Busch, Andrew Cameron, Leslie Liu-Bujalski, Henry Yu, Hui Tian, Mark Shearman, Anna Quattropani, Bruno Permanne, Christoph Wiessner, Dirk Beher
<h3>Background</h3> The basal ganglia play an important role in drug dependence. Excitatory glutamatergic projections from the cerebral cortex innervate at striatal medium spiny neuron, which also receives modulatory dopaminergic and cholinergic projections. This anatomical relationship suggests that chronic elevation of dopamine by METH may disrupt release both glutamate acetylcholine (ACh). Investigations our laboratory have demonstrated treatment mice with results a long-lasting...