A5018001257- Alzheimer's disease research and treatments
- Drug Transport and Resistance Mechanisms
- Barrier Structure and Function Studies
- Prion Diseases and Protein Misfolding
- Advancements in Transdermal Drug Delivery
- Advanced Drug Delivery Systems
- Cholinesterase and Neurodegenerative Diseases
- Neurological Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Gut microbiota and health
- Neuroscience and Neuropharmacology Research
- Monoclonal and Polyclonal Antibodies Research
- Cellular transport and secretion
- Advanced Neuroimaging Techniques and Applications
- Surfactants and Colloidal Systems
- Intracerebral and Subarachnoid Hemorrhage Research
- Amino Acid Enzymes and Metabolism
- Dementia and Cognitive Impairment Research
- Medical Imaging Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Ferroptosis and cancer prognosis
- S100 Proteins and Annexins
- Analytical Methods in Pharmaceuticals
- Peroxisome Proliferator-Activated Receptors
- Supramolecular Self-Assembly in Materials
University of Minnesota System
2023-2025
University of Minnesota
2014-2024
Mayo Clinic
2010-2023
Rosalind Franklin University of Medicine and Science
2020
Mayo Clinic in Arizona
2018
Florida Agricultural and Mechanical University
1998-2013
WinnMed
2008-2010
Laboratory of Molecular Genetics
2007
University of Iowa
2005
The inflammatory tumoral-immune response alters the physiology of tumor microenvironment, which may attenuate genomic instability. In addition to inducing immune responses, several pathogenic bacteria produce genotoxins. However extent microbial contribution microenvironment biology remains unknown. We utilized Cancer Genome Atlas, (TCGA) breast cancer data perform a novel experiment utilizing unmapped and mapped RNA sequencing read evidence minimize laboratory costs effort. Our objective...
Parkinson's disease (PD) is a common neurodegenerative disorder characterized primarily by motor and non-motor gastrointestinal (GI) deficits. GI symptoms' including compromised intestinal barrier function often accompanies altered gut microbiota composition deficits in PD. Therefore, this study, we set to investigate the role of epithelial dysfunction on symptom generation using rotenone-induced mouse model We found that while six weeks 10 mg/kg chronic rotenone administration oral gavage...
Aberrant insulin signaling constitutes an early change in Alzheimer's disease (AD). Insulin receptors (IR) and low-density lipoprotein receptor-related protein-1 (LRP-1) are expressed brain capillary endothelial cells (BCEC) forming the blood-brain barrier (BBB). There, may regulate function of LRP-1 Aβ clearance from brain. Changes IR-β at BBB AD not well understood. Herein, we identified a reduction cerebral cerebrovascular levels 9-month-old male female 3XTg-AD (PS1M146V, APPSwe,...
Abstract Targeting therapeutic or diagnostic proteins to the nervous system is limited by presence of blood–brain barrier. We report that a F(ab′) 2 fragment monoclonal antibody against fibrillar human Aβ42 polyamine (p)‐modified has increased permeability at barrier, comparable binding antigen, and in vitro amyloid plaques Alzheimer’s disease (AD) transgenic mouse brain sections. Intravenous injection pF(ab′) 4.1 AD demonstrated efficient targeting throughout brain, whereas unmodified did...
Alzheimer's disease (AD) is characterized by significant neurodegeneration in the cortex and hippocampus; intraneuronal tangles of hyperphosphorylated tau protein; accumulation beta-amyloid (Abeta) proteins 40 42 brain parenchyma as well cerebral vasculature. The current understanding that AD initiated neuronal Abeta due to their inefficient clearance at blood-brain-barrier (BBB), places neurovascular unit epicenter pathophysiology. objective this study investigate cellular mechanisms...
Several different monoclonal antibodies (mAbs) have been actively developed in the field of Alzheimer's disease (AD) for basic science and clinical applications; however, binding kinetics many mAbs with beta-amyloid peptides (Abeta) are poorly understood. A panel Abeta recognition sites, including our plaque-binding antibody (IgG4.1), a peptide-capturing (11A50), two classical (6E10 4G8) used immunohistochemistry, were chosen characterization their to monomeric fibrillar forms Abeta40 using...
Mounting evidence suggests that the pathological hallmarks of Alzheimer's disease (AD), neurofibrillary tangles and parenchymal amyloid plaques, are downstream reflections neurodegeneration caused by intraneuronal accumulation amyloid-β proteins (Aβ), particularly Aβ42 Aβ40. While neurotoxicity more amyloidogenic but less abundant is well documented, effect Aβ40 on neurons has been understudied. The expression in presymptomatic AD brain ten times greater than Aβ42. However, Aβ40:42 ratio...
Impaired brain clearance of amyloid-beta peptides (Aβ) 40 and 42 across the blood–brain barrier (BBB) is believed to be one pathways responsible for Alzheimer’s disease (AD) pathogenesis. Hyperinsulinemia prevalent in type II diabetes was shown damage cerebral vasculature increase Aβ accumulation AD brain. However, there no clarity on how aberrations peripheral insulin levels affect This study describes, first time, an intricate relation between plasma transport at BBB. Upon administration...
Recent studies suggest that apolipoprotein A-I (ApoA-I), the major protein constituent of high-density lipoprotein particles, plays a critical role in preserving cerebrovascular integrity and reducing Alzheimer's risk. ApoA-I present brain is thought to be primarily derived from peripheral circulation. Although plasma-to-brain delivery claimed handled by blood-cerebrospinal fluid barrier (BCSFB), contribution blood-brain (BBB), which serves as portal for brain, cannot ruled out. In this...
Abstract Cerebrovascular inflammation is prevalent in a majority of Alzheimer’s patients. Inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), circulating the plasma have been shown to cause blood-brain barrier (BBB) endothelium lining cerebral microvasculature. The BBB has implicated increase toxic Aβ accumulation within disease (AD) brain. TNF-alpha peripheral circulation can aggravate amyloid-beta (Aβ) peptides In current study, we that exposure leads an Aβ42 mice and...
Gut bacteria influence host intestinal phenotype in ways that impact drug absorption and metabolism. By comparing colonic tissue from germ-free mice to those colonized with human microbiota, this study evaluates microbiota-driven differences gene expression P-gp efflux capacity. Transcriptomic analysis revealed upregulation of genes coding ATP-binding cassette transporters (Abcb1a, Abcb1b), BCRP (Abcg2), MRP3 (Abcc3), along increased solute carriers MCT1 (Slc16a1) OCTN2 (Slc22a5)....
Alzheimer's disease (AD) affects 40 million individuals globally and is characterized by the accumulation of amyloid-beta (Aβ) proteins, which aggregate form plaques. BBB dysfunction drives AD cerebrovascular pathology integrity maintained neurovascular unit (NVU). Specifically, within NVU, cerebral endothelial cells maintain vascular homeostasis. In this study, we isolated endothelial-enriched regions interest (ROIs) using Nanostring GeoMx digital spatial profiler employed a deconvolution...
Abstract The apolipoprotein E (apoE) ε4 allele is the primary genetic risk factor for late‐onset Alzheimer's disease (AD). ApoE in brain produced primarily by astrocytes; once secreted from these cells, apoE binds lipids and forms high‐density lipoprotein (HDL)‐like particles. Accumulation of amyloid‐β protein (Aβ) a key hallmark AD, thought to initiate pathogenic cascade leading neurodegeneration dementia. level lipidation state affect Aβ aggregation clearance pathways. Elevated levels...
DATA REPORT article Front. Neurosci., 01 March 2016Sec. Neurogenomics Volume 10 - 2016 | https://doi.org/10.3389/fnins.2016.00071
Transdermal delivery of melatonin would be advantageous in the treatment sleep disorders considering short biological half-life and its variable bioavailability via oral route. This study looked at suitable penetration enhancers for transdermal permeation melatonin. The was enhanced by all saturated unsaturated fatty acids across both rat porcine skin. There a parabolic relationship between carbon chain length enhancement For skin, maximum flux observed with undecanoic acid (45.33 microg...