A5058417020- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Phosphodiesterase function and regulation
- Ion channel regulation and function
- Renin-Angiotensin System Studies
- Amino Acid Enzymes and Metabolism
- Cholinesterase and Neurodegenerative Diseases
- Tryptophan and brain disorders
- Molecular Biology Techniques and Applications
- Genetics and Neurodevelopmental Disorders
- Nicotinic Acetylcholine Receptors Study
- Neuropeptides and Animal Physiology
- Epilepsy research and treatment
- Estrogen and related hormone effects
- Epigenetics and DNA Methylation
- Genetic Associations and Epidemiology
- CRISPR and Genetic Engineering
- Photoreceptor and optogenetics research
- Signaling Pathways in Disease
- Mycobacterium research and diagnosis
- Amyotrophic Lateral Sclerosis Research
- Alzheimer's disease research and treatments
- Cancer-related molecular mechanisms research
- Chemical synthesis and alkaloids
- Neuroinflammation and Neurodegeneration Mechanisms
AstraZeneca (United States)
2016-2025
Tufts University
2015-2025
University of Pittsburgh
2025
Imperial College London
2002-2024
New England Research Institutes
2024
Pfizer (United States)
2010-2023
AstraZeneca (Brazil)
2018-2023
University of New Brunswick
2023
University of Toronto
2023
Jnana Therapeutics (United States)
2020-2022
The disrupted in schizophrenia 1 ( DISC1 ) gene is a candidate susceptibility factor for schizophrenia, but its mechanistic role the disorder unknown. Here we report that encoding phosphodiesterase 4B PDE4B by balanced translocation subject diagnosed with and relative chronic psychiatric illness. PDEs inactivate adenosine 3′,5′-monophosphate (cAMP), second messenger implicated learning, memory, mood. We show interacts UCR2 domain of elevation cellular cAMP leads to dissociation from an...
There is compelling clinical literature implicating a role for cytokines in the pathophysiology of major depressive disorder (MDD). Interleukin-6 (IL-6) and interleukin-1β (IL-1β) are pleiotropic inflammatory that have been reported to be elevated patients with MDD. The present studies were undertaken investigate relationship between IL-6 IL-1β animal models depressive-like behavior. Analysis brain tissue homogenates cortex rats subjected chronic stress paradigms revealed levels protein...
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder typically characterized by insoluble inclusions of hyperphosphorylated TDP-43. The mechanisms underlying toxic TDP-43 accumulation are not understood. Persistent activation p38 mitogen-activated protein kinase (MAPK) implicated in ALS. However, it unclear how MAPK affects proteinopathy. Here, we show that p38α inhibition reduces pathological phosphorylation, aggregation, cytoplasmic mislocalization, and...
Following several recent reports that suggest dual cAMP and cGMP phosphodiesterase 10A (PDE10A) inhibitors may present a novel mechanism to treat positive symptoms of schizophrenia, we sought extend the preclinical characterization two such compounds, papaverine [1-(3,4-dimethoxybenzyl)-6,7-dimethoxyisoquinoline] MP-10 [2-{[4-(1-methyl-4-pyridin-4-yl-1<i>H</i>-pyrazol-3-yl)phenoxy]methyl}quinoline], in variety vivo vitro assays. Both these compounds were active range antipsychotic models,...
Estrogen, in addition to its genomic effects brain, causes rapid and reversible changes synaptic operations. We report here that these acute actions are due selective activation of an actin-signaling cascade normally used the production long-term potentiation (LTP). or a agonist steroid's β-receptor, caused modest increase fast glutamatergic transmission pronounced facilitation LTP adult hippocampal slices; both were completely eliminated by latrunculin, toxin prevents actin filament...
Disrupted-in-Schizophrenia-1 ( DISC1 ), identified by positional cloning of a balanced translocation (1;11) with the breakpoint in intron 8 large Scottish pedigree, is associated range neuropsychiatric disorders including schizophrenia. To model this mutation mice, we have generated Disc1 tr transgenic mice expressing 2 copies truncated encoding first exons using bacterial artificial chromosome (BAC). With partial simulation human situation, discovered phenotypes series novel features not...
Positive allosteric modulators (PAMs) of metabotropic glutamate receptor subtype 5 (mGlu5) enhance <i>N</i>-methyl-d-aspartate function and may represent a novel approach for the treatment schizophrenia. ADX47273 [<i>S</i>-(4-fluoro-phenyl)-{3-[3-(4-fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-piperidin-1-yl}-methanone], recently identified potent selective mGlu5 PAM, increased (9-fold) response to threshold concentration (50 nM) in fluorometric Ca<sup>2+</sup> assays (EC<sub>50</sub> = 170 human...
Positive allosteric modulators (PAMs) of the M4 muscarinic acetylcholine receptor (mAChR) represent a novel approach for treatment psychotic symptoms associated with schizophrenia and other neuropsychiatric disorders. We recently reported that selective PAM VU0152100 produced an antipsychotic drug-like profile in rodents after amphetamine challenge. Previous studies suggest enhanced cholinergic activity may also improve cognitive function reverse deficits observed reduced signaling through...
Abstract Human induced pluripotent stem cells (hiPSCs) are a powerful model of neural differentiation and maturation. We present hiPSC transcriptomics resource on corticogenesis from 5 iPSC donor 13 subclonal lines across 9 time points over broad conditions: self-renewal, early neuronal differentiation, precursor (NPCs), assembled rosettes, differentiated cells. identify widespread changes in the expression both individual features global patterns transcription. next demonstrate that...