A5032228482- Neuroscience and Neuropharmacology Research
- Adipose Tissue and Metabolism
- Stress Responses and Cortisol
- Circadian rhythm and melatonin
- Parkinson's Disease Mechanisms and Treatments
- Mitochondrial Function and Pathology
- Animal Behavior and Welfare Studies
- Genetic Neurodegenerative Diseases
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Plant Gene Expression Analysis
- Photoreceptor and optogenetics research
- Neuroendocrine regulation and behavior
- Regulation of Appetite and Obesity
- Genetics and Physical Performance
- RNA Interference and Gene Delivery
- Fungal and yeast genetics research
- Retinal Development and Disorders
- Phosphodiesterase function and regulation
- Biochemical Analysis and Sensing Techniques
- Ubiquitin and proteasome pathways
- Neuroscience of respiration and sleep
- Autophagy in Disease and Therapy
- Thermoregulation and physiological responses
- Retinal and Macular Surgery
Escape Therapeutics (United States)
2020-2024
Amgen (United States)
2016
Biological E (India)
2014
California Institute of Technology
2005-2011
University of California, Los Angeles
1998-2010
UCLA Medical Center
2000
University of California, Santa Barbara
1968-1993
St George's, University of London
1988
Drexel University
1988
Texas Children's Hospital
1988
Brain injury, genetic manipulations, and pharmacological treatments can result in alterations of motor skills mice. Fine coordination balance be assessed by the beam walking assay. The goal this test is for mouse to stay upright walk across an elevated narrow a safe platform. This takes place over 3 consecutive days: 2 days training 1 day testing. Performance on quantified measuring time it traverse number paw slips that occur process. Here we report protocol used our laboratory,...
At excitatory synapses, the postsynaptic scaffolding protein density 95 (PSD-95) couples NMDA receptors (NMDARs) to Ras GTPase-activating SynGAP. The close association of SynGAP and NMDARs suggests that may have an important role in NMDAR-dependent activation signaling pathways, such as MAP kinase pathway, synaptic plasticity. To explore this issue, we examined long-term potentiation (LTP), p42 MAPK (ERK2) signaling, spatial learning mice with a heterozygous null mutation gene (SynGAP(-/+))....
The membrane‐associated guanylate kinases (MAGUKs) PSD‐95, PSD‐93 and SAP102 are thought to have crucial roles in both AMPA receptor trafficking formation of NMDA receptor‐associated signalling complexes involved synaptic plasticity. While PSD‐93, appear similar trafficking, it is not known whether these MAGUKs also functionally To explore this issue we examined several properties basal transmission the hippocampal CA1 region PSD‐95 mutant mice compared ability a number different stimulation...
Abstract Pathogenic mutations in LRRK2 cause Parkinson’s disease (PD). The G2019S variant is the most common, which results abnormally high kinase activity. Compounds that target activity are currently being developed and tested clinical trials. We recently found causes mitochondrial DNA (mtDNA) damage treatment with multiple classes of inhibitors at concentrations associated dephosphorylation reversed mtDNA to healthy control levels. Because maintaining normal function heterozygous carriers...
SynGAP, a prominent Ras/Rap GTPase-activating protein in the postsynaptic density, regulates timing of spine formation and trafficking glutamate receptors cultured neurons. However, molecular mechanisms by which it does this are unknown. Here, we show that synGAP is key regulator morphology adult mice. Heterozygous deletion was sufficient to cause an excess mushroom spines brains, indicating involved steady-state regulation actin mature spines. Both Ras- Rac-GTP levels were elevated...
Brain injury, genetic manipulations, and pharmacological treatments can result in alterations of motor skills mice. Fine coordination balance be assessed by the beam walking assay. The goal this test is for mouse to stay upright walk across an elevated narrow a safe platform. This takes place over 3 consecutive days: 2 days training 1 day testing. Performance on quantified measuring time it traverse number paw slips that occur process. Here we report protocol used our laboratory,...
The effect of estrogen replacement on several parameters energy balance was investigated in ovariectomized rats tested during the dark phase their diurnal cycle. Estrogen replacement, either as 17 beta-estradiol or beta-estradiol-3-benzoate via subcutaneous Silastic capsules, associated with elevated rates heat production and dry loss relative to untreated controls. treatment reduced body mass retarded fur growth. effects could not be attributed these differences growth locomotor activity....
synGAP is a neuron-specific Ras and Rap GTPase-activating protein (GAP) found in high concentrations the postsynaptic density (PSD) fraction from mammalian forebrain. We have previously shown that, situ PSD or recombinant form Sf9 cell membranes, phosphorylated by Ca(2+)/calmodulin-dependent kinase II (CaMKII), another prominent component of PSD. Here, we show that (r-synGAP), lacking 102 residues at N terminus, can be purified soluble cyclin-dependent 5 (CDK5) as well CaMKII....
Activation of metabotropic glutamate receptors (mGluRs) with the group I mGluR selective agonist (R,S)-3,5-dihydroxyphenylglycine (DHPG) induces a long-term depression (LTD) excitatory synaptic transmission in CA1 region hippocampus. Here we investigated potential roles pre- and postsynaptic processes DHPG-induced LTD at synapses onto hippocampal pyramidal cells mouse mGluRs DHPG, but not ACPD, induced both Schaffer collateral/commissural fiber associational/commissural CA3 cells. was...
Densin is an abundant scaffold protein in the postsynaptic density (PSD) that forms a high-affinity complex with αCaMKII and α-actinin. To assess function of densin, we created mouse line null mutation gene encoding it ( LRRC7 ). Homozygous knock-out mice display wide variety abnormal behaviors are often considered endophenotypes schizophrenia autism spectrum disorders. At cellular level, loss densin results reduced levels α-actinin brain selective reduction localization mGluR5 DISC1 PSD...
Autophagy is the primary process for recycling cellular constituents through lysosomal degradation. In addition to nonselective autophagic engulfment of cytoplasm, autophagosomes can recognize specific cargo by interacting with ubiquitin-binding autophagy receptors such as SQSTM1/p62 (sequestosome 1). This selective form important degrading aggregation-prone proteins prominent in many neurodegenerative diseases. We carried out a high content image-based siRNA screen (4 8 per gene) modulators...
Pathogenic variants in the leucine-rich repeat kinase 2 (LRRK2) gene have been identified that increase risk for developing Parkinson's disease a dominantly inherited fashion. These pathogenic variants, of which G2019S is most common, cause abnormally high activity, and compounds inhibit this activity are being pursued as potentially disease-modifying therapeutics. Because LRRK2 regulates important cellular processes, inhibitors can selectively target variant while sparing normal could offer...
1. The effects of warming and cooling the spinal cord hypothalamus on operant thermoregulatory behaviour posture have been studied in pig at neutral cold ambient temperatures.2. Cooling increased decreased rate obtaining thermal reinforcement. response to began with onset stimulus persisted for up 5 min followed by a diminution during remaining 15 cooling. peak this ;on' was greater lower temperature. heating small reduction reinforcement.3. related changes temperature only cervical region...
<ns4:p>A common pathological hallmark of age-related neurodegenerative diseases is the intracellular accumulation protein aggregates such as α-synuclein in Parkinson’s disease, TDP-43 ALS, and tau Alzheimer’s disease. Enhancing clearance aggregation-prone proteins a plausible strategy for slowing progression there great interest identifying molecular targets that control turnover. One main routes degradation through proteasome, multisubunit protease degrades have been tagged with...
A common pathological hallmark of age-related neurodegenerative diseases is the intracellular accumulation protein aggregates such as α-synuclein in Parkinson's disease, TDP-43 ALS, and tau Alzheimer's disease. Enhancing clearance aggregation-prone proteins a plausible strategy for slowing progression there great interest identifying molecular targets that control turnover. One main routes degradation through proteasome, multisubunit protease degrades have been tagged with polyubiquitin...
Sensitization to inflammatory pain is a pathological form of neuronal plasticity that poorly understood and treated. Here we examine the role SH3 domain postsynaptic density 95 (PSD95) by using mice carry single amino‐acid substitution in polyproline‐binding site. Testing multiple forms found sensitization inflammation was specifically attenuated. The response required recruitment phosphatidylinositol‐3‐kinase‐C2α SH3‐binding site PSD95. In wild‐type mice, wortmannin or peptide competition...
ABSTRACT Background A common genetic mutation that causes Parkinson's disease (PD) is the G2019S LRRK2 mutation. precision medicine approach selectively blocks only excess kinase activity of mutant allele could yield a safe and effective treatment for PD. Objective To determine selective leucine‐rich repeat 2 (LRRK2) inhibitor as compared to nonselective in blood subjects with idiopathic PD on two biomarkers, pSer935 pThr73 Rab10. Methods Blood was collected from 13 or without one healthy...