A5031147990- Alzheimer's disease research and treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Neuroscience and Neuropharmacology Research
- Nicotinic Acetylcholine Receptors Study
- Receptor Mechanisms and Signaling
- Peroxisome Proliferator-Activated Receptors
- Neurogenesis and neuroplasticity mechanisms
- Neurotransmitter Receptor Influence on Behavior
- Tryptophan and brain disorders
- Memory and Neural Mechanisms
- Mosquito-borne diseases and control
- Adipose Tissue and Metabolism
- Nerve injury and regeneration
- Parkinson's Disease Mechanisms and Treatments
- Natural Antidiabetic Agents Studies
- Ion channel regulation and function
- Infectious Encephalopathies and Encephalitis
- HIV Research and Treatment
- Heme Oxygenase-1 and Carbon Monoxide
- Prion Diseases and Protein Misfolding
- Signaling Pathways in Disease
- Hippo pathway signaling and YAP/TAZ
- Stress Responses and Cortisol
- Neurological disorders and treatments
The University of Texas Medical Branch at Galveston
2015-2024
Institute for Neurodegenerative Disorders
2018
Galveston College
2014-2017
Metabiota (United States)
2015
Addiction Research Foundation
2014
The University of Texas at Austin
2010
Baylor College of Medicine
1996-2006
Allergan (Ireland)
1989
Alzheimer's Disease (AD) is the most common of senile dementias, prevalence which increasing rapidly, with a projected 14 million affected worldwide by 2025. The signal transduction mechanisms that underlie learning and memory derangements in AD are poorly understood. β-Amyloid (Aβ) peptides elevated brain tissue patients principal component amyloid plaques, major criterion for postmortem diagnosis disease. Using acute organotypic hippocampal slice preparations, we demonstrate Aβ peptide...
Recent findings suggest that tau oligomers, which form before neurofibrillary tangles (NFTs), are the true neurotoxic entities in neurodegenerative tauopathies, including Alzheimer's disease (AD). Studies animal models of tauopathy oligomers play a key role eliciting behavioral and cognitive impairments. Here, we used novel oligomer-specific monoclonal antibody (TOMA) for passive immunization mice expressing mutant human tau. A single dose TOMA administered either intravenously or...
Abstract Vascular mechanisms of Alzheimer’s disease (AD) may constitute a therapeutically addressable biological pathway underlying dementia. We previously demonstrated that soluble pathogenic forms tau (tau oligomers) accumulate in brain microvasculature AD and other tauopathies, including prominently microvascular endothelial cells. Here we show accumulates cells P301S(PS19) mice modeling tauopathy drives AD-like deficits. Microvascular impairments were partially negated by selective...
Abstract: The mitogen‐activated protein kinase ERK has recentlybecome a focus of studies synaptic plasticity and learning memory. Dueto the prominent role potassium channels in regulating electricalproperties membranes, modulation these by could play animportant mediating learning‐related CNS.Kv4.2 is Shal‐type channel that passes an A‐type current islocalized to dendrites cell bodies hippocampus. sequence ofKv4.2 contains several consensus sites for phosphorylation. In presentstudies, we...
The α7 nicotinic acetylcholine receptor is highly expressed in hippocampus and cholinergic projection neurons from the basal forebrain, structures that are particularly vulnerable to ravages of Alzheimer's disease. Previous work suggests β-amyloid peptide can interact with receptors, although nature this interaction has not been well characterized. To test whether activate we these receptors inXenopus oocytes performed two-electrode voltage clamp recordings, characterizing response 1–42...
Familial Alzheimer's disease-associated mutations in presenilin 1 or 2 amyloid precursor protein result elevated β-amyloid, β-amyloid accumulation, and plaque formation the brains of affected individuals. By crossing transgenic mice carrying A246E mutation with plaque-producing K670N/M671L (Tg2576), we show that co-expression both mutant transgenes results acceleration accumulation associative learning deficits. At 5 months age no detectable pathology, animals are impaired contextual fear...
Early Alzheimer's disease (AD) is marked by cholinergic hypofunction, neuronal marker loss, and decreased nicotinic acetylcholine receptor (nAChR) density from the cortex hippocampus. α7 nAChRs expressed on projection neurons target regions have been implicated in neuroprotection against β-amyloid (Aβ) toxicity maintenance of septohippocampal phenotype. We tested role that perform etiology early AD genetically deleting nAChR subunit Tg2576 mouse model for assessing animals cognitive function...
Abstract Collapsin response mediator protein 2 (CRMP2) is an abundant brain‐enriched that can regulate microtubule assembly in neurons. This function of CRMP2 regulated by phosphorylation glycogen synthase kinase 3 (GSK3) and cyclin‐dependent 5 (Cdk5). Here, using novel phosphospecific antibodies, we demonstrate at Ser522 (Cdk5‐mediated) increased Alzheimer’s disease (AD) brain, while expression the closely related isoform CRMP4 are not altered. In addition, Cdk5 GSK3 sites cortex...
In Alzheimer's disease (AD), the pathological accumulation of tau appears to be a downstream effect amyloid β protein (Aβ). However, relationship between these two proteins and memory loss is unclear. this study, we evaluated specific removal oligomers in aged Tg2576 mice by passive immunotherapy using oligomer-specific monoclonal antibody. Removal reversed deficits accelerated plaque deposition brain. Surprisingly, Aβ*56 levels decreased, suggesting link Aβ promotion cognitive decline. The...
J. Neurochem. (2012) 120 , 440–452. Abstract Intracellular deposition of fibrillar aggregates α‐synuclein (αSyn) characterizes neurodegenerative diseases such as Parkinson’s disease (PD) and dementia with Lewy bodies. However, recent evidence indicates that small αSyn oligomeric precede fibril formation may be the most neurotoxic species can found extracellularly. This new has changed view pathological aggregation from a self‐contained cellular phenomenon to an extracellular event prompted...
We previously reported that the peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone (RSG) improved hippocampus-dependent cognition in Alzheimer's disease (AD) mouse model, Tg2576. RSG had no effect on wild-type littermate cognitive performance. Since extracellular signal-regulated protein kinase mitogen-activated (ERK MAPK) is required for many forms of learning and memory are affected AD, since both PPARγ ERK MAPK key mediators insulin signaling, current study tested...
Soluble oligomeric aggregates of the amyloid-beta (A beta) peptide are believed to be most neurotoxic A beta species affecting brain in Alzheimer disease (AD), a terminal neurodegenerative disorder involving severe cognitive decline underscored by initial synaptic dysfunction and later extensive neuronal death CNS. Recent evidence indicates that oligomers recruited at synapse, oppose expression long-term potentiation (LTP), perturb intracellular calcium balance, disrupt dendritic spines,...
Summary Alzheimer's disease (AD) is a terminal age‐associated dementia characterized by early synaptic dysfunction and late neurodegeneration. Although the presence of plaques fibrillar aggregates amyloid beta peptide (Aβ) signature AD, evidence suggests that preplaque small oligomeric Aβ promotes both neuronal death. We found young Tg2576 transgenic mice, which accumulate develop cognitive impairments prior to plaque deposition, have high central nervous system (CNS) activity calcineurin...
It is now recognized that astrocytes participate in synaptic communication through intimate interactions with neurons. A principal mechanism the release of gliotransmitters (GTs) such as ATP, D-serine and most notably, glutamate, response to astrocytic calcium elevations. We others have shown amyloid-β (Aβ), toxic trigger for Alzheimer's disease (AD), interacts hippocampal α7 nicotinic acetylcholine receptors (nAChRs). Since α7nAChRs are highly permeable expressed on astrocytes, we...