A5025207687- Alzheimer's disease research and treatments
- Blood properties and coagulation
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Genetic Neurodegenerative Diseases
- Autophagy in Disease and Therapy
- Endoplasmic Reticulum Stress and Disease
- Microtubule and mitosis dynamics
- Wnt/β-catenin signaling in development and cancer
- Cholinesterase and Neurodegenerative Diseases
- Parkinson's Disease Mechanisms and Treatments
- Hereditary Neurological Disorders
- Cellular transport and secretion
- Skin and Cellular Biology Research
- Calpain Protease Function and Regulation
- Aluminum toxicity and tolerance in plants and animals
- Erythrocyte Function and Pathophysiology
- Cell death mechanisms and regulation
- Signaling Pathways in Disease
- Protein Kinase Regulation and GTPase Signaling
- Cancer-related gene regulation
- Botulinum Toxin and Related Neurological Disorders
- Genetics, Aging, and Longevity in Model Organisms
- Prion Diseases and Protein Misfolding
- Adipokines, Inflammation, and Metabolic Diseases
University of Rochester Medical Center
2016-2025
University of Rochester
2016-2025
Film Independent
2016
University of Ottawa
2016
University of Maryland, Baltimore
2014
McGill University
2014
The University of Texas MD Anderson Cancer Center
2014
University of Alabama at Birmingham
2002-2011
University of Alabama
2001
Durham Technical Community College
1996
Histone deacetylase 6 (HDAC6), a unique cytoplasmic deacetylase, likely plays role in neurodegeneration by coordinating cell responses to abnormal protein aggregation. Here, we provide vitro and vivo evidence that HDAC6 interacts with tau, microtubule-associated forms neurofibrillary tangles Alzheimer's disease. This interaction is mediated the microtubule-binding domain on tau Ser/Glu tetradecapeptide HDAC6. Treatment tubacin, selective inhibitor of tubulin deacetylation activity HDAC6, did...
Abstract: The p38 mitogen‐activated protein kinase is a stress‐activated enzyme responsible for transducing inflammatory signals and initiating apoptosis. In the Alzheimer's disease (AD) brain, increased levels of phosphorylated (active) were detected relative to age‐matched normal brain. Intense phospho‐p38 immunoreactivity was associated with neuritic plaques, neuropil threads, neurofibrillary tangle‐bearing neurons. antibody against recognized many same structures as an aberrantly...
Paired helical filaments (PHFs) are the major structural elements of Alzheimer's disease neurofibrillary lesions, and these formed from hyperphosphorylated brain tau known as PHF-tau. Recent studies showed that many previously identified phosphorylated residues in PHF-tau also phosphate acceptor sites fetal rapidly processed adult tau. However, Ser262 has been suggested to be uniquely a key regulator binding microtubules. For reasons, we generated monoclonal antibody (12E8) specific for 12E8...
Glycogen synthase kinase-3β (GSK3β) is a central figure in Wnt signaling, which its activity controlled by regulatory binding proteins. Here we show that proteins outside the pathway also control of GSK3β. DNA damage induced camptothecin, activates tumor suppressor p53, was found to activate This activation occurred phosphorylation-independent mechanism involving direct GSK3β confined nucleus where p53 localized, and mutated (R175H) bound but did not Activation GSK3 promoted responses...
There is significant evidence that energy production impairment and mitochondrial dysfunction play a role in the pathogenesis of Huntington disease. Nonetheless, specific defects due to presence mutant huntingtin have not been fully elucidated. To determine effects on production, thorough analysis respiration, ATP functioning respiratory complexes was carried out clonal striatal cells established from HdhQ7 (wild-type) HdhQ111 (mutant knock-in) mouse embryos. Mitochondrial respiration were...
Site-specific phosphorylation of tau negatively regulates its ability to bind and stabilize microtubule structure. Although is a substrate glycogen synthase kinase 3beta (GSK3beta), the exact sites on that are phosphorylated by this in situ have not yet been established, effect these events tau-microtubule interactions fully elucidated. GSK3beta phosphorylates both primed unprimed tau, but only significantly decrease microtubules. The focus present study determining importance...
Glycogen synthase kinase 3beta (GSK3beta) phosphorylates substrates, including the microtubule-associated protein tau, at both primed and unprimed epitopes. GSK3beta phosphorylation of tau negatively regulates tau-microtubule interactions; however differential effects epitopes on is unknown. To examine how this impacts function, R96A mutant was used, a mutation that prevents substrates sites. Both GSK3beta-R96A phosphorylated efficiently in situ. However, expression resulted significantly...
Abstract : The modulation of tau phosphorylation in response to insulin was examined human neuroblastoma SH‐SY5Y cells. Insulin treatment resulted a transient increase followed by decrease that correlated directly with sequential activation and deactivation glycogen synthese kinase‐3β (GSK‐3β). insulin‐induced concurrent GSK‐3β rapid (<2 min) transient, associated increased tyrosine GSK‐3β. corresponded an the association Fyn kinase GSK‐3β, immunoprecipitated from cells treated for 1 min...
Tissue transglutaminase (tTG) is a calcium-dependent enzyme that catalyzes the posttranslational modification of proteins by transamidation specific polypeptide-bound glutamine residues. Previous in vitro studies have demonstrated transamidating activity tTG requires calcium and inhibited GTP. To investigate endogenous regulation tTG, quantitative situtransglutaminase (TG) assay was developed. Treatment human neuroblastoma SH-SY5Y cells with retinoic acid (RA) resulted significant increase...
The in vitro degradation of microtubule-associated protein 2 (MAP-2) and spectrin by the calcium-dependent neutral protease calpain was studied. Five major results are reported. First, MAP-2 isolated from twice-cycled microtubules (2 X MT MAP-2) extremely sensitive to calpain-induced hydrolysis. Even at an enzyme-to-substrate ratio (wt/wt) 1:200, significantly degraded calpain. Second, purified total brain heat-stable fraction (total more resistant hydrolysis compared with MAP-2. Third,...
Deficient signaling by insulin, as occurs in diabetes, is associated with impaired brain function, and diabetes an increased prevalence of Alzheimer's disease. One the hallmark pathological characteristics disease presence neurofibrillary tangles containing hyperphosphorylated tau, a microtubule-associated protein. Therefore, we tested hypothesis that insulin depletion caused administration streptozotocin may cause tau hyperphosphorylation mouse using site-specific phosphorylation-dependent...
Idiopathic pulmonary fibrosis (IPF) is a deadly progressive disease with few treatment options. Transglutaminase 2 (TG2) multifunctional protein, but its function in unknown.To determine the role of TG2 fibrosis.The fibrotic response to bleomycin was compared between wild-type and knockout mice. transglutaminase-catalyzed isopeptide bond expression examined formalin-fixed human lung biopsy sections by immunohistochemistry from patients IPF. In addition, primary fibroblasts were used study...