A5101875808- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Neurobiology and Insect Physiology Research
- Genetics and Neurodevelopmental Disorders
- Nerve injury and regeneration
- Protein Kinase Regulation and GTPase Signaling
- Signaling Pathways in Disease
- Insect and Pesticide Research
- Neurology and Historical Studies
- Nuclear Receptors and Signaling
- Ubiquitin and proteasome pathways
- Neuropeptides and Animal Physiology
- Tryptophan and brain disorders
- Cellular transport and secretion
- Mitochondrial Function and Pathology
- Cholinesterase and Neurodegenerative Diseases
- PI3K/AKT/mTOR signaling in cancer
- Genetic Syndromes and Imprinting
- Phosphodiesterase function and regulation
- Cardiac electrophysiology and arrhythmias
- Neonatal and fetal brain pathology
- Photoreceptor and optogenetics research
- Lipid Membrane Structure and Behavior
- Nicotinic Acetylcholine Receptors Study
Brown University
2010-2024
Allen Institute for Brain Science
2024
Rockefeller University
2010-2011
The University of Texas Medical Branch at Galveston
2003
Providence College
2002
University of Virginia
1987-2000
Yale University
1996
General Medical Council
1893
University College London
1893
Antiinflammatory drugs achieve their therapeutic actions at least in part by regulation of cytokine formation. A “cytokine hypothesis” depression is supported the observation that depressed individuals have elevated plasma levels certain cytokines compared with healthy controls. Here we investigated a possible interaction between antidepressant agents and antiinflammatory on antidepressant-induced behaviors p11, biochemical marker depressive-like states responses. We found widely used...
Angelman syndrome (AS) is a neurodevelopment disorder characterized by severe cognitive impairment and high rate of autism. AS caused disrupted neuronal expression the maternally inherited Ube3A ubiquitin protein ligase, required for proteasomal degradation proteins implicated in synaptic plasticity, such as activity-regulated cytoskeletal-associated (Arc/Arg3.1). Mice deficient maternal express elevated levels Arc response to activity, which coincides with severely impaired long-term...
Signaling mediated by brain-derived neurotrophic factor (BDNF), which is supported the postsynaptic scaffolding protein PSD-95, has antidepressant effects. Conversely, clinical depression associated with reduced BDNF signaling. We found that peptidomimetic compounds bind to PSD-95 promoted signaling receptor TrkB in hippocampus and depression-like behaviors mice. The CN2097 Syn3 both PDZ3 domain of also binds an α-helical region protein. two mouse models stress-induced depression; had...
Receptor tyrosine kinases (RTKs) have long been associated with proliferation in non-neural cells, although they are also expressed postmitotic neurons. We demonstrate that insulin-like growth factor-1 (IGF-1) induces within seconds a large, tyrosine- kinase-dependent increase calcium channel currents cerebellar granule Separation of subtypes reveals that, while P, Q, and R channels unaffected, N L activities strongly potentiated at specific membrane voltages: triple depolarized potentials,...
The insulin-like growth factor-1 (IGF-1)/receptor tyrosine kinase recently has been shown to mediate neuronal survival and potentiate the activity of specific calcium channel subtypes; requires Akt, a serine/threonine kinase. We demonstrate here that Akt mediates IGF-1-induced potentiation L currents, but not N channels. Transient expression wild-type, dominant–negative, constitutively active forms in cerebellar granule neurons causes, respectively, no change IGF-1/L potentiation, complete...
Two members of the Gα i family G proteins form complexes with EGFR and adaptor protein Gab1 to mediate activation Akt.
Significance Heterotrimeric Gαi proteins are known to transduce G protein-coupled receptor signals. We have identified a role for in mediating brain-derived neurotrophic factor (BDNF)–tropomyosin-related kinase B (TrkB) signaling. BDNF dysfunction contributes the pathophysiology of depression. In stress model depression Gαi1 and Gαi3 downregulated hippocampus, limbic structure associated with major depressive disorder. show that Gαi1/Gαi3 required TrkB downstream signaling, knockout mice...
Tropomyosin receptor kinase B (TrkB) signaling plays a pivotal role in dendritic growth and spine formation to promote learning memory. The activity-dependent release of brain-derived neurotrophic factor at synapses binds pre- or postsynaptic TrkB resulting the strengthening synapses, reflected by long-term potentiation. Postsynaptically, association density protein-95 with enhances phospholipase Cγ-Ca2+/calmodulin-dependent protein II phosphatidylinositol 3-kinase-mechanistic target...
The kainate receptor subunit KA2 does not form functional homomeric channels despite its structural similarity to the glutamate 5-7subunits and high agonist binding affinity in vitro assays. In this study, we first demonstrate that receptors fail reach plasma membrane then identify molecular mechanisms preventing surface expression. Specifically, show subunits homooligomeric are confined endoplasmic reticulum (ER). We that, both heterologous expression systems primary neurons, intracellular...
Kainate receptors have been implicated in excitotoxic neuronal death induced by diseases such as epilepsy and stroke. Actinfilin, a synaptic member of the BTB-Kelch protein family, is known to bind actin cytoskeleton. However, little understood about its function at synapse. Here, we report that actinfilin able GluR6, kainate-type glutamate receptor subunit, target GluR6 for degradation. Like many members acts substrate adaptor, binding Cullin 3 (Cul3) linking E3 ubiquitin-ligase complex. We...
Dopaminergic neurons in the ventral tegmental area, major midbrain nucleus projecting to motor cortex, play a key role skill learning and cortex synaptic plasticity. Dopamine D1 D2 receptor antagonists exert parallel effects system: they impair reduce long-term potentiation. Traditionally, modulate adenylyl cyclase activity cyclic adenosine monophosphate accumulation opposite directions via different G-proteins bidirectionally protein kinase A (PKA), leading distinct physiological behavioral...
It is widely accepted that overactivation of NMDA receptors, resulting in calcium overload and consequent mitochondrial dysfunction retinal ganglion neurons, plays a significant role promoting neurodegenerative disorders such as glaucoma. Calcium has been shown to initiate transient hyperpolarization the membrane potential triggering burst reactive oxygen species leading apoptosis. Strategies enhance cell survival signaling pathways aimed at preventing this adverse may provide novel...
We previously reported that expression of polyglutamine-expanded huntingtin induces apoptosis via c-Jun amino-terminal kinase (JNK) activation in HN33 cells (Liu, Y. F. (1998) <i>J. Biol. Chem.</i> 273, 28873–28822). Extending this study, we now demonstrate a role mixed-lineage 2 (MLK2), JNK activator, huntingtin-mediated neuronal toxicity. find normal interacts with MLK2, whereas the polyglutamine expansion interferes interaction. Similar to huntingtin, MLK2 also and cells. Co-expression...