A5030637514- Signaling Pathways in Disease
- HIV Research and Treatment
- Nerve injury and regeneration
- Neuroscience and Neuropharmacology Research
- Toxin Mechanisms and Immunotoxins
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuropeptides and Animal Physiology
- Peptidase Inhibition and Analysis
- Alzheimer's disease research and treatments
- Genetics and Neurodevelopmental Disorders
- Prion Diseases and Protein Misfolding
- Mitochondrial Function and Pathology
- Ion channel regulation and function
- Trypanosoma species research and implications
- Chromosomal and Genetic Variations
- RNA Interference and Gene Delivery
- 3D Printing in Biomedical Research
- CRISPR and Genetic Engineering
- Parkinson's Disease Mechanisms and Treatments
- Computational Drug Discovery Methods
- Pluripotent Stem Cells Research
- RNA Research and Splicing
- Receptor Mechanisms and Signaling
- Neurotransmitter Receptor Influence on Behavior
- Tryptophan and brain disorders
National Institutes of Health
2015-2025
National Institute of Neurological Disorders and Stroke
2016-2025
Nanotherapeutics (United States)
2024
Johns Hopkins Medicine
1995-2023
Johns Hopkins University
2006-2023
University of Virginia Health System
2022
Neurological Surgery
2022
Hudson Institute
2022
National Institute of Dental and Craniofacial Research
2012
Federation for the Humanities and Social Sciences
2010
Immunosuppressants FK506 and cyclosporin A inhibit neurotoxicity of N-methyl-D-aspartate in primary cortical cultures, while having no effect on quisqualate- kainate-mediated neurotoxicity. Rapamycin completely reverses the neuroprotective FK506. Both NMDA-elicited/nitric oxide-mediated increases cGMP levels cultures. has sodium nitroprusside-induced cGMP. In a stably transfected human kidney 293 cell line overexpressing gene encoding nitric oxide synthase [L-arginine, NADPH:oxygen...
Huntington's Disease (HD) is caused by expansion of a CAG repeat within putative open reading frame recently identified gene, IT15. We have examined the expression gene's protein product using antibodies developed against N-terminus and an internal epitope. Both antisera recognize 350 kDa protein, predicted size, indicating that translated into polyglutamine. The HD widely expressed, most highly in neurons brain. There no enrichment striatum, site greatest pathology HD. Within neurons,...
Human endogenous retrovirus-K is activated in the cortical neurons of patients with amyotrophic lateral sclerosis, and expression viral envelope protein mouse brain reproduces clinical pathological phenotype this disease.
The underlying mechanisms by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to and long-term neurological manifestations remains obscure. We aimed characterize the neuropathological changes in patients with disease 2019 determine pathophysiological mechanisms. In this autopsy study of brain, we characterized vascular pathology, neuroinflammatory cellular humoral immune responses immunohistochemistry. All died during first wave pandemic from March July 2020. were...
Although immunosuppressant immunophilin ligands promote neurite outgrowth in vitro, their neurotrophic activities are clearly independent of immunosuppressive activity. In the present report, a novel nonimmunosuppressive ligand, GPI-1046 (3-(3-pyridyl)-1-propyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-pyrrolidinecarboxylate+ ++) is described. bound to FK506 binding protein-12 and elicited from sensory neuronal cultures with picomolar potency maximal effects comparable nerve growth factor....
The immunosuppressant drug FK506 acts by binding to receptor proteins, FK506-binding proteins (FKBPs), which in turn can bind and regulate a Ca(2+)-dependent phosphatase, calcineurin, Ca2+ release channel, the ryanodine receptor. Based on our findings regeneration models that levels of FKBPs during neural parallel those growth-associated protein GAP43, calcineurin substrate regulates neurite extension, we examined effects PC12 rat pheochromocytoma cells sensory ganglia. enhances outgrowth...
The immunophilin FK506 binding protein 12 (FKBP12) is associated with and modulates the ryanodine receptor calcium release channel of skeletal muscle. Ryanodine has amino acid homology functional similarity another intracellular Ca2+ channel, inositol 1,4,5-trisphosphate (IP3R). In present study we show that highly purified preparations IP3R contain FKBP12. complex these two proteins disrupted by immunosuppressants rapamycin, both which are known to bind FKBP12 high affinity. Disrupting...
Immune responses in lymphocytes require cellular accumulation of large amounts calcium (Ca 2+ ) from extracellular sources. In the T cell tumor line Jurkat, receptors for Ca -releasing messenger inositol 1,4,5-trisphosphate (IP 3 were localized to plasma membrane (PM). Capping receptor-CD3 complex, which is associated with signal transduction, was accompanied by capping IP receptors. The receptor on cells appears be responsible entry that initiates proliferative responses.
Objective: The aim of this study was to measure the protein concentration and biological activity HIV-1 Tat in cerebrospinal fluid (CSF) individuals on suppressive antiretroviral therapy (ART). Design: CSF collected from 68 HIV-positive ART with plasma viral load less than 40 copies/ml, 25 HIV-negative healthy controls. Duration HIV infection ranged 4 more 30 years. Methods: levels were evaluated by an ELISA. RNA quantified exosomes isolated CSF, followed western blot or quantitative reverse...
Alzheimer's disease (AD), one of the leading neurodegenerative disorders older adults, which causes major socioeconomic burdens globally, lacks effective therapeutics without significant side effects. Besides hallmark pathology amyloid plaques and neurofibrillary tangles (NFTs), it has been reported that cyclin-dependent kinase 5 (Cdk5), a critical neuronal kinase, is hyperactivated in AD brains is, part, responsible for above pathology. Here we show modified truncated 24-aa peptide (TFP5),...
Abstract Background Uncontrolled seizures in patients with gliomas have a significant impact on quality of life and morbidity, yet the mechanisms through which these tumors cause remain unknown. Here, we hypothesize that active metabolite d-2-hydroxyglutarate (d-2-HG) produced by IDH-mutant enzyme leads to metabolic disruptions surrounding cortical neurons consequently promote seizures. Methods We use complementary study vitro neuron-glial cultures electrographically sorted human tissue from...
Human endogenous retroviruses (HERVs) are ancestral viral relics that constitute nearly 8% of the human genome. Although normally silenced, most recently integrated provirus HERV-K (HML-2) can be reactivated in certain cancers. Here, we report pathological expression HML-2 malignant gliomas both cerebrospinal fluid and tumor tissue was associated with a cancer stem cell phenotype poor outcomes. Using single-cell RNA-Seq, identified glioblastoma cellular populations elevated transcripts...
TAR DNA-binding protein 43 (TDP-43) proteinopathy in brain cells is the hallmark of amyotrophic lateral sclerosis (ALS) but its cause remains elusive. Asparaginase-like-1 (ASRGL1) cleaves isoaspartates, which alter folding and susceptibility to proteolysis. ASRGL1 gene harbors a copy human endogenous retrovirus HML-2, whose overexpression contributes ALS pathogenesis. Here we show that expression was diminished samples by RNA sequencing, immunohistochemistry, western blotting. TDP-43...
In countries infected with HIV clade B, some patients develop a rapidly progressive dementia that if untreated results in death. regions of the world C, only milder forms cognitive impairment have been recognized. HIV-infected macrophages are principal mediators dementia. however, efficiently infects and found brains C-infected patients. release Tat protein, which may act directly on neurons to cause toxicity. We released from Tat-expressing cells was at least 1000-fold more toxic than...
The inositol 1,4,5-trisphosphate receptor (IP3R) associated with plasma membranes of lymphocytes differs in terminal sugar content and binding specificity from the cerebellar receptor, which is localized to endoplasmic reticulum. Lectin column chromatography reveals that 30% IP3R thymus contains sialic acid, reflecting a membrane association, contrast 5% IP3R. fractions Jurkat microsomes cerebellum phosphate specificity. has lower affinity for IP3 but higher 1,3,4,5-tetrakisphosphate, may...