A5100693033- Amyotrophic Lateral Sclerosis Research
- Alzheimer's disease research and treatments
- Adipose Tissue and Metabolism
- Mitochondrial Function and Pathology
- Neurogenetic and Muscular Disorders Research
- Diet and metabolism studies
- Parkinson's Disease Mechanisms and Treatments
- Lysosomal Storage Disorders Research
- RNA Research and Splicing
- Dementia and Cognitive Impairment Research
- Glycogen Storage Diseases and Myoclonus
- Endoplasmic Reticulum Stress and Disease
- Cellular transport and secretion
- S100 Proteins and Annexins
- Plant biochemistry and biosynthesis
- Cancer, Hypoxia, and Metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- Frailty in Older Adults
- Carbohydrate Chemistry and Synthesis
- Cholesterol and Lipid Metabolism
- GDF15 and Related Biomarkers
- Nuclear Receptors and Signaling
- Pancreatic function and diabetes
- Nutrition and Health in Aging
- Metabolism, Diabetes, and Cancer
Orlando Health
2024
Saint Louis University
2018-2024
Florida College
2024
University of Florida
2024
University of California, Irvine
2023
Washington University in St. Louis
2022-2023
Neurological Surgery
2023
University of California, San Diego
2013-2023
UCLouvain Saint-Louis Brussels
2020-2023
Saint Louis University
2021
Objective— The cytosolic form of Cu/Zn-containing superoxide dismutase (SOD1) has peroxidase activity, with H 2 O used as a substrate to oxidize other molecules. We examined properties the extracellular SOD (SOD3), major isoform in vessel wall, by using recombinant SOD3 and an vivo model atherosclerosis. Methods Results— In presence HCO 3 − , reacted produce hydroxyl radical adduct spin trap 5-diethoxyphosphoryl-5methyl-1-pyrroline N -oxide (DEMPO). SOD1 were inactivated dose- time-dependent...
Abstract Haploinsufficiency of GRN causes frontotemporal dementia (FTD). The locus produces progranulin (PGRN), which is cleaved to lysosomal granulin polypeptides. function granulins and why their absence neurodegeneration are unclear. Here we discover that PGRN-deficient human cells murine brains, as well frontal lobes from -mutation FTD patients have increased levels gangliosides, glycosphingolipids contain sialic acid. In these tissues, enzymes catabolize gangliosides were normal, but...
Niche signals maintain stem cells in a prolonged quiescence or transiently activate them for proper regeneration1. Altering balanced niche signalling can lead to regenerative disorders. Melanocytic skin nevi human often display excessive hair growth, suggesting cell hyperactivity. Here, using genetic mouse models of nevi2,3, we show that dermal clusters senescent melanocytes drive epithelial exit and change their transcriptome composition, potently enhancing renewal. Nevus distinct...
Endoplasmic reticulum-associated degradation of the enzyme 3-hydroxy-3-methylglutaryl-CoA reductase represents one mechanism by which cholesterol synthesis is controlled in mammalian cells. The key reaction this binding to Insig proteins endoplasmic reticulum, stimulated precursor lanosterol. Conversion lanosterol requires removal three methyl groups, consumes nine molecules dioxygen. Here, we report that oxygen deprivation (hypoxia) slows demethylation and its metabolite...
Inflammation and oxidative stress have been implicated in the pathophysiology of Parkinson's disease (PD) inhibition microglial activation attenuates degeneration dopaminergic (DA) neurons animal models PD. Loss-of-function mutations parkin gene, which encodes an E3 ubiquitin ligase, cause autosomal recessive parkinsonism. While most studies on Parkin focused its function neurons, here we demonstrate that mRNA protein is detectable brain-resident microglia peripheral macrophages. Using...
The extracellular superoxide dismutase (ecSOD) plays an important role in atherosclerosis and endothelial function by modulating levels of the anion (O2*-) space. Although heparan sulfate proteoglycan is ligand for ecSOD, little known about other biological binding partners ecSOD. goal this study was to identify novel proteins that interact with A yeast two-hybrid screening a human aorta cDNA library using ecSOD as bait identified fibulin-5 predominant protein Further analysis showed domain...
Significance Mutations in the GRN gene cause frontotemporal dementia, a devastating neurological disease. The majority of these mutations are nonsense and frameshift mutations. Here, we generated knockin mouse model with Grn mutation corresponding to most prevalent human disease mutation, R493X . We show that mice harboring this phenocopy progranulin-deficient mice, triggers mRNA decay and, as consequence, low production However, truncated mutant protein would be produced from allele is...
Abstract Neurofilament light chain (NfL) has been associated with cognitive status in multiple neurodegenerative conditions. Studies about plasma NfL and decline older adults are still limited. 504 (median age 75 years) who expressed memory complaints were selected from the Multidomain Alzheimer’s Preventive Trial (MAPT) classified as normal cognition (NC) or mild impairment (MCI). Cognitive functions measured mini mental state examination (MMSE) composite score (CCS) over a 4-year period....
Physical activity (PA) demonstrated benefits on brain health, but its relationship with blood biomarkers of neurodegeneration remains poorly investigated. We explored the cross-sectional associations PA concentrations neurofilament light chain (NFL) and beta amyloid (Aβ)42/40. further examined whether interaction between these was longitudinally related to cognition. Four-hundred sixty-five nondemented older adults engaged in an interventional study who had a concomitant assessment levels...
Abstract The neural functions of adropin, a secreted peptide highly expressed in the brain, have not been investigated. In humans, adropin is astrocytes and peaks during critical postnatal periods brain development. Gene enrichment analysis transcripts correlating with expression suggests processes relevant to aging-related neurodegenerative diseases that vary age dementia state, possibly indicating survivor bias. people aged <40 y ‘old-old’ (>75 y) diagnosed dementia, correlates...
Blood biomarkers can offer valuable and easily accessible indicators of normal biological processes, pathogenic conditions, responses to therapeutic interventions. Recent studies found that levels neurofilament light chain (NfL) in the blood are associated with mortality three European cohorts older adults (median ages 73, 93, 100 years). Whether similar associations exist younger other ethnic groups is currently not known.
Abstract Background Cognition is closely associated with physical function. Although high brain amyloid-β (Aβ) deposition and neurofilament light chain (NfL) are cognitive gait speed decline, relationships of combined plasma Aβ NfL profiles functions in older adults remain unknown. The research aim this study was to investigate the prospective associations adults. Methods Participants ( n = 452, aged 76 ± 5 years) who had both data collected from Multidomain Alzheimer’s Preventive Trial...
Embolization of the middle meningeal artery (MMA) is a safe and effective adjunct in treatment chronic subdural hematoma. While prior authors describe use coils to assist embolization by preventing reflux through eloquent collaterals, we de- scribe further open MMA, allowing administration greater amounts embolisate for more robust embolization. The objective this study was demonstrate that helical can safely MMA following polyvinyl alcohol (PVA) particles. This allows be administered into...
Abstract The secreted peptide adropin is highly expressed in human brain tissues and correlates with RNA proteomic risk indicators for dementia. Here we report that plasma concentrations predict cognitive decline the Multidomain Alzheimer Preventive Trial (ClinicalTrials.gov Identifier, NCT00672685; mean age 75.8y, SD = 4.5 years, 60.2% female, n 452). Cognitive ability was evaluated using a composite score (CCS) assessed four domains: memory, language, executive function, orientation....
In the initial assessment of a headache patient, several dangerous secondary etiologies must be considered. A thorough history and physical examination, along with comprehensive differential diagnosis may alert physician to particularly when it is accompanied by certain clinical features. Evaluation workup include complete neurological consideration neuroimaging, serum/spinal fluid analysis if indicated. Careful attention patients’ examination will guide diagnostic work-up management. this...
Objectives To determine the integration of signalling pathways associated with two recognized Kaposi's sarcoma (KS) growth factors, oncostatin M (OSM) and basic fibroblast factor (bFGF), in induction KS cell proliferation. Design methods We used protein kinase assays, protein-DNA interactions AP-1 luciferase assays to study extracellular signal-regulated (FRK), Janus (JAK)-Stat Jun (JNK) AIDS-derived cells during stimulation OSM bFGF. Results Treatment OSM-induced activation...
Glycogen storage disease type Ib (GSD-Ib) is caused by a deficiency in the ubiquitously expressed glucose 6-phosphate transporter (Glc-6-PT). Glc-6-PT activity has been shown to be critical liver and kidney where disrupts homeostasis. GSD-Ib patients also have defects neutrophil respiratory burst, chemotaxis, calcium flux. They manifest neutropenia, but whether bone marrow underlies myeloid dysfunctions remains controversial. To address this, we transferred from Glc-6-PT-deficient...