A5061180703- Pharmacological Receptor Mechanisms and Effects
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuropeptides and Animal Physiology
- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Receptor Mechanisms and Signaling
- Cholinesterase and Neurodegenerative Diseases
- Intensive Care Unit Cognitive Disorders
- Prion Diseases and Protein Misfolding
- Ion channel regulation and function
- Anesthesia and Neurotoxicity Research
- DNA Repair Mechanisms
- 3D Printing in Biomedical Research
- Neuroscience and Neural Engineering
- Neurological disorders and treatments
- Axial and Atropisomeric Chirality Synthesis
- Anesthesia and Sedative Agents
- Tryptophan and brain disorders
- Genetics and Neurodevelopmental Disorders
- Genetic Neurodegenerative Diseases
- CRISPR and Genetic Engineering
- Nicotinic Acetylcholine Receptors Study
- Adenosine and Purinergic Signaling
- PARP inhibition in cancer therapy
- Enhanced Recovery After Surgery
Johns Hopkins Medicine
2017-2024
Johns Hopkins University
2017-2024
National Eye Institute
2023
National Institutes of Health
2023
University of South Florida
2012-2019
Florida College
2012-2014
Genetika
2013
Institute of Pharmacology Russian Academy of Medical Sciences
2013
West Virginia University
2012
In this work, we describe the fabrication and working of a modular microsystem that recapitulates functions "Neurovascular Unit". The microdevice comprised vertical stack poly(dimethylsiloxane) (PDMS) neural parenchymal chamber separated by vascular channel via microporous polycarbonate (PC) membrane. housed mixture neurons (~4%), astrocytes (~95%), microglia (~1%). was lined with layer rat brain microvascular endothelial cell line (RBE4). Cellular components in showed viability (>90%)....
Abstract The spread of prion‐like protein aggregates is a common driver pathogenesis in various neurodegenerative diseases, including Alzheimer's disease (AD) and related Tauopathies. Tau pathologies exhibit clear progressive spreading pattern that correlates with severity. Clinical observation combined complementary experimental studies has shown preformed fibrils (PFF) are seeds propagate pathology by entering cells templating misfolding aggregation endogenous Tau. While several cell...
Microglial cells play a critical role in the neuroinflammatory response that accompanies various diseases of central nervous system, such as ischemic stroke, and ATP is major signaling molecule regulating these to pathophysiological conditions. Experiments were carried out determine effects afobazole on microglial function identify molecular mechanisms by which affects cells. Afobazole was found inhibit migration UTP chemoattraction concentration-dependent manner. Inhibition either σ-1 or...
Alzheimer's disease (AD) is a progressive neurodegenerative and the leading cause of senile dementia in United States. Accumulation amyloid-<i>β</i> (A<i>β</i>) effects this peptide on microglial cells contribute greatly to etiology AD. Experiments were carried out determine whether pan-selective <i>σ</i>-receptor agonist afobazole can modulate response cytotoxic A<i>β</i> fragment, A<i>β</i><sub>25–35</sub>. Treatment with decreased activation A<i>β</i>, as indicated by reduced membrane...
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by continual decline of cognitive function. No therapy has been identified that can effectively halt or reverse its progression. One hallmark AD accumulation the amyloid-<i>β</i> peptide (A<i>β</i>), which alone induces neuronal injury via various mechanisms. Data presented here demonstrate prolonged exposure (1–24 hours) rat cortical neurons to A<i>β</i><sub>25–35</sub> results in an increase basal intracellular...
Postoperative cognitive dysfunction (POCD) is a significant complication of surgery, particularly in elderly patients. Emerging researches showed that long non-coding RNA (lncRNA) may play vital role the pathogenesis POCD. Here we aimed to identify potential key lncRNAs involved development LncRNA and mRNA expression profiles hippocampal tissues from POCD control mice were analyzed by microarray assay. Gene ontology (GO) KEGG pathway enrichment analyses conducted probe functions dysregulated...
Alzheimer's disease (AD) is the leading cause of dementia worldwide, but there are limited therapeutic options and no current cure. While involvement microglia in AD has been highly appreciated, role other innate adaptive immune cells remains largely unknown, partly due to their scarcity heterogeneity. This study aimed non-microglial wild type AD-transgenic mouse brains across different ages. Our results uncovered presence a unique CD8+ T cell population that were selectively increased aging...
Afobazole is an anxiolytic medication that has been previously shown to be neuroprotective both in vitro and vivo. However, the mechanism(s) by which afobazole can enhance neuronal survival remain poorly understood. Experiments were carried out determine whether decrease intracellular calcium overload associated with ischemia acidosis effects of are mediated via interaction compound σ receptors. Fluorometric Ca<sup>2+</sup> imaging was used resolve how application affects handling cortical...
The AAA+ adenosine triphosphatase (ATPase) Thorase plays a critical role in controlling synaptic plasticity by regulating the expression of surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Bidirectional sequencing exons ATAD1, gene encoding Thorase, cohort patients with schizophrenia and healthy controls revealed rare variants. These variants caused defects glutamatergic signaling impairing AMPAR internalization recycling mouse primary cortical neurons. This...
Activation of sigma receptors at delayed time points has been shown to decrease injury following ischemic stroke. The mixed σ1/σ2 receptor agonist, 5-ethoxy-2-[2-(morpholino)-ethylthio]benzimidazole (afobazole), provides superior long-term outcomes compared other σ ligands in the rat middle cerebral artery occlusion (MCAO) stroke model. Experiments using MCAO model were carried out determine molecular mechanism involved beneficial effects afobazole. Administration afobazole (3 mg/kg)...
The spread of prion-like protein aggregates is believed to be a common driver pathogenesis in many neurodegenerative diseases. Accumulated tangles filamentous Tau are considered pathogenic lesions Alzheimer's disease (AD) and related Tauopathies, including progressive supranuclear palsy, corticobasal degeneration. pathologies these illnesses exhibits clear hierarchical spreading pattern that correlates with severity
Currently, the only Food and Drug Administration–approved treatment of acute stroke is recombinant tissue plasminogen activator, which must be administered within 6 hours after onset. The pan-selective <i>σ</i>-receptor agonist <i>N</i>,<i>N</i>′-di-<i>o</i>-tolyl-guanidine (<i>o</i>-DTG) has been shown to reduce infarct volume in rats middle cerebral artery occlusion, even when 24 stroke. DTG derivatives were synthesized develop novel compounds with greater potency than <i>o</i>-DTG....
Stroke continues to be a leading cause of death and serious long-term disability. The lack therapeutic options for treating stroke at delayed time points (≥ 6 hr post-stroke) remains challenge. sigma receptor agonist, afobazole, an anxiolytic used clinically in Russia, has been shown reduce neuronal glial cell injury following ischemia acidosis; both which have play important roles ischemic stroke. However, the mechanism(s) responsible this cytoprotection remain unknown. Experiments were...
Summary Toxic cellular insults activate the nuclear protein poly (ADP-ribose) (PAR) polymerase-1 (PARP-1) to initiate parthanatos, a regulated cell death program. PAR acts as signal by translocating from nucleus cytosol, where it activates next steps in parthanatic cascade. How translocates cytosol is not known. Here we show that PARylation and binding histone H1.2 enables act carrier, transporting out of cytosol. Knocking down expression via CRISPR/Cas9 knockout reduces translocation after...
Stroke is the second cause of death and leading serious long‐term disability. Ischemic stroke often overlaps with diseases involving amyloid‐β (Aβ), such as Alzheimer’s cerebral amyloid angiopathy. These comorbidities lead to potentiated responses that ultimately result in vascular dementia. The mechanism(s) contributing this potentiation remain poorly understood. One key player pathobiology Aβ toxicity dysregulation intracellular calcium ([Ca 2+ ] i ) homeostasis. Experiments were carried...