A5090593770- Alzheimer's disease research and treatments
- Tuberculosis Research and Epidemiology
- Neuroinflammation and Neurodegeneration Mechanisms
- Mycobacterium research and diagnosis
- Neurological Disease Mechanisms and Treatments
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Bacterial Genetics and Biotechnology
- Dementia and Cognitive Impairment Research
- RNA and protein synthesis mechanisms
- Protease and Inhibitor Mechanisms
- Bacteriophages and microbial interactions
- Prion Diseases and Protein Misfolding
- Antibiotic Resistance in Bacteria
- Blood Coagulation and Thrombosis Mechanisms
- Biotin and Related Studies
- Intracerebral and Subarachnoid Hemorrhage Research
- Nuclear Receptors and Signaling
- S100 Proteins and Annexins
- Neuropeptides and Animal Physiology
- Glycosylation and Glycoproteins Research
- Neurological Disorders and Treatments
- Enzyme Structure and Function
- Immunodeficiency and Autoimmune Disorders
- Monoclonal and Polyclonal Antibodies Research
- Memory and Neural Mechanisms
Stony Brook University
2008-2023
McLaughlin Research Institute
2012-2014
Cornell University
2012-2014
University of California, Irvine
2007
Air Force Medical University
2005
Oklahoma Medical Research Foundation
2005
Cerebral microvascular amyloid beta protein (Abeta) deposition and associated neuroinflammation is increasingly recognized as an important component leading to cognitive impairment in Alzheimer's disease related cerebral angiopathy disorders. Transgenic mice expressing the vasculotropic Dutch/Iowa (E693Q/D694N) mutant human Abeta precursor brain (Tg-SwDI) accumulate abundant fibrillar deposits exhibit robust neuroinflammation. In present study, we investigated effect of anti-inflammatory...
Alzheimer's disease (AD) is characterized by three primary pathologies in the brain: amyloid plaques, neurofibrillary tangles, and neuron loss. Mouse models have been useful for studying components of AD but are limited their ability to fully recapitulate all pathologies. We crossed APPSwDI transgenic mouse, which develops β (Aβ)-protein deposits only, with a nitric oxide synthase 2 (NOS2) knock-out no AD-like pathology. APPSwDI/NOS2 −/− mice displayed impaired spatial memory compared mice,...
Increasing evidence indicates that cerebrovascular dysfunction plays a pathogenic role in Alzheimer's dementia (AD). Amyloid-β (Aβ), peptide central to the pathogenesis of AD, has profound vascular effects mediated, for most part, by reactive oxygen species produced enzyme NADPH oxidase. The mechanisms linking Aβ oxidase-dependent oxidative stress have not been identified, however. We report scavenger receptor CD36, membrane glycoprotein binds Aβ, is essential and neurovascular induced 1–40...
Accumulation of amyloid-β in cerebral blood vessels occurs familial and sporadic forms amyloid angiopathy is a prominent feature Alzheimer disease. However, the functional correlates vascular pathology induced by mechanisms involved have not been fully established.We used male transgenic mice expressing Swedish, Iowa, Dutch mutations precursor protein (Tg-SwDI) to examine effect on cerebrovascular structure function. Somatosensory cortex flow was monitored laser-Doppler flowmetry...
Alzheimer's disease is characterized by two primary pathological features: amyloid plaques and neurofibrillary tangles. The interconnection between tau aggregates of intense interest, but mouse models have yet to reveal a direct interrelationship. We now show that NO may be key factor connects pathologies. Genetic removal synthase 2 in mice expressing mutated precursor protein results hyperphosphorylation tau, its redistribution the somatodendritic compartment cortical hippocampal neurons,...
Research on the human pathogen Mycobacterium tuberculosis (Mtb) would benefit from novel tools for regulated gene expression. Here we describe characterization and application of a synthetic riboswitch-based system, which comprises mycobacterial promoter transcriptional control riboswitch translational control. The system was used to induce repress heterologous protein overexpression reversibly, create conditional knockdown, expression in macrophage infection model. Unlike existing systems...
Background and Purpose— Amyloid-β (Aβ), a peptide that accumulates in the brain circulates blood of patients with Alzheimer disease, alters regulation cerebral flow may contribute to dysfunction underlying dementia. However, contributions circulating Aβ1–40 vascular have not been elucidated. Methods— We used transgenic mice overexpressing mutated forms amyloid precursor protein which is elevated (Tg-2576) or only (Tg-SwDI). Mice were equipped cranial window, increase induced by neural...
Cerebral microvascular amyloid-β (Aβ) protein deposition is emerging as an important contributory factor to neuroinflammation and dementia in Alzheimer's disease related familial cerebral amyloid angiopathy disorders. In particular, deposition, but not parenchymal amyloid, more often correlated with dementia. Recently, we generated transgenic mice ( Tg-SwDI ) expressing the vasculotropic Dutch (E693Q)/Iowa (D694N) mutant human Aβ precursor brain that accumulate abundant fibrillar deposits....
The amyloid β-protein precursor (AβPP) is best known as the parent molecule to β-peptide that accumulates in brains of patients with Alzheimer's disease. Secreted isoforms AβPP contain Kunitz proteinase inhibitor domain are analogous previously identified cell-secreted protease nexin-2 (PN2). Although PN2/AβPP enriched brain and circulating blood platelets, little understood its physiological function potential role disease processes outside generation. We hypothesized potent inhibition...
Novel amyloid precursor protein transgenic mice, which contain the Swedish as well vasculotropic Dutch and Iowa mutations (Tg-SwDI), were used to investigate mechanisms of antibody-mediated clearance amyloid-beta (Abeta) from brain. Export Abeta-DI peptide across blood-brain barrier is severely reduced because mutations. Therefore, dependent on antibodies entering In this report, we immunized Tg-SwDI mice with various antigens, including Abeta40-DI, Abeta42, an Abeta epitope vaccine....
The amyloid beta-protein precursor (AbetaPP) is best recognized as the to Abeta peptide that accumulates in brains of patients with Alzheimer's disease, but less known about its physiological functions. Isoforms AbetaPP contain a Kunitz-type serine proteinase inhibitor (KPI) domain are expressed brain and, outside CNS, circulating blood platelets. Recently, we showed KPI-containing forms regulates cerebral thrombosis vivo (Xu et al., 2005, 2007). Amyloid like protein-2 (APLP2), closely...
Outer membrane lipids in pathogenic mycobacteria are important for virulence and survival. Although the biosynthesis of these has been extensively studied, mechanisms responsible their assembly outer not understood. In study Gram-negative assembly, protein-protein interactions define transport mechanisms, but analogous have explored mycobacteria. Here we identified with lipid protein LprG. Using site-specific photo-cross-linking live mycobacteria, mapped three major interaction interfaces...
Trehalose glycolipids are found in many bacteria the suborder Corynebacterineae, but methyl-branched acyltrehaloses exclusive to virulent species such as human pathogen Mycobacterium tuberculosis. In M. tuberculosis, acyltransferase PapA3 catalyzes formation of diacyltrehalose (DAT), enzymes responsible for downstream reactions leading final product, polyacyltrehalose (PAT), have not been identified. The PAT biosynthetic gene locus is similar that another trehalose glycolipid, sulfolipid 1....
Cerebrovascular deposition of fibrillar amyloid beta-protein (Abeta), a condition known as cerebral angiopathy (CAA), is prominent pathological feature Alzheimer's disease (AD) and related disorders. Accumulation vascular Abeta implicated in promoting local neuroinflammation, causes marked degeneration smooth muscle cells, can lead to loss vessel wall integrity with hemorrhage. However, the relationship between Abeta-induced inflammatory responses localized cytotoxicity remains...
Human apolipoprotein (ApoE) genotype influences the development of Alzheimer's disease and cerebral amyloid angiopathy (CAA). Specific mutations within amyloid-β protein (Aβ) peptide have been identified that cause familial forms CAA. However, effect APOE on accumulation CAA mutant Aβ in brain is not well understood. In present study, we determined how human ApoE3 or ApoE4 influence transgenic mice (Tg-SwDI) accumulate Dutch/Iowa (E22Q/D23N) brain, primarily form fibrillar microvascular...
The study of the bacterial periplasm requires techniques with sufficient spatial resolution and sensitivity to resolve components processes within this subcellular compartment. Peroxidase-mediated biotinylation has enabled targeted labeling proteins compartments mammalian cells. We investigated whether methodology could be applied periplasm. In study, we demonstrated that peroxidase-mediated can performed in mycobacteria Escherichia coli. To eliminate detection artifacts from natively...
<i>Background/Aims:</i> There is increased amyloid-β protein precursor (AβPP) expression and (Aβ) production in the brain shortly following cerebral ischemic stroke rodent models. It has been postulated that this may seed amyloid deposition brain. On other hand, it remains unclear how ischemia affects preexisting Aβ deposits Here we determine consequences of focal on existing pathology Tg-SwDI transgenic mice. <i>Methods:</i> At 12 months age, mice were subjected to...
Human apolipoprotein (ApoE) genotype influences the development of Alzheimer's disease and cerebral amyloid angiopathy (CAA), where ε4 allele increases ε2 decreases risk for developing disease. Specific mutations within amy
(