A5064826111- Muscle Physiology and Disorders
- Amyotrophic Lateral Sclerosis Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Adipose Tissue and Metabolism
- Cardiomyopathy and Myosin Studies
- Tryptophan and brain disorders
- RNA Interference and Gene Delivery
- S100 Proteins and Annexins
- Neonatal and fetal brain pathology
- Neurological disorders and treatments
- Organometallic Complex Synthesis and Catalysis
- Neurological Disease Mechanisms and Treatments
- CRISPR and Genetic Engineering
- Drug Transport and Resistance Mechanisms
- Acute Ischemic Stroke Management
- Mitochondrial Function and Pathology
- Fatty Acid Research and Health
- Exercise and Physiological Responses
- Cell Image Analysis Techniques
- Nuclear Receptors and Signaling
- Spinal Cord Injury Research
- Neuroscience and Neuropharmacology Research
- Neonatal Respiratory Health Research
Jain Foundation
2017
University of Maryland, Baltimore
2017
Charles River Laboratories (Netherlands)
2017
University of Eastern Finland
2006-2008
Institute for Molecular Science
2007
Pasadena City College
2007
Pyrrolidine dithiocarbamate (PDTC) is a clinically tolerated inhibitor of nuclear factor-κB (NF-κB), antioxidant and antiinflammatory agent, which provides protection in brain ischemia models. In neonatal hypoxia–ischemia model, PDTC activates Akt reduces activation glycogen synthase kinase 3β (GSK-3β). Because chronic inflammation, oxidative stress, increased GSK-3β activity are features Alzheimer's disease (AD) pathology, we tested whether pathology improves cognitive function transgenic...
This work demonstrates how increased activity of copper-zinc superoxide dismutase (SOD1) paradoxically boosts production toxic reactive oxygen species (ROS) in the intermembrane space (IMS) mitochondria. Even though SOD1 is a cytosolic enzyme, fraction it found IMS, where thought to provide protection against oxidative damage. We that controls cytochrome c-catalyzed peroxidation vitro when available. The presence significantly rate ROS mitoplasts, which are devoid outer membrane and IMS. In...
Abstract Background Granulocyte colony stimulating factor (GCSF) is protective in animal models of various neurodegenerative diseases. We investigated whether pegfilgrastim, GCSF with sustained action, a mouse model amyotrophic lateral sclerosis (ALS). ALS fatal disease manifestations upper and lower motoneuron death muscle atrophy accompanied by inflammation the CNS periphery. Methods Human mutant G93A superoxide dismutase (SOD1) mice were treated pegfilgrastim starting at presymptomatic...
beta-Amyloid (Abeta) polypeptide plays a critical role in the pathogenesis of Alzheimer's disease (AD), which is characterized by progressive decline cognitive functions, formation Abeta deposits and neurofibrillary tangles, loss neurons. Increased genetic production or direct intracerebral administration animal models results deposition, gliosis, impaired functions. Whether aging renders brain prone to whether inflammation required for Abeta-induced learning deficits unclear. We show that...
Pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear transcription factor κ-B (NF-κB) and antioxidant, has beneficial effects in animal models various diseases, including arthritis, brain ischemia, spinal cord injury, Alzheimer9s disease, Duchenne muscular dystrophy. Because inflammation oxidative damage are also hallmarks amyotrophic lateral sclerosis (ALS), we studied the effect oral PDTC treatment on G93A-superoxide dismutase 1 (SOD1) transgenic (TG) rat model human ALS observed...
Abstract The identification of a dysferlin‐deficient animal model that accurately displays both the physiological and behavior aspects human dysferlinopathy is critical for evaluation potential therapeutics. Disease progression in mice relatively mild, compared to debilitating disease which manifests impairment particular motor functions. Since there are no other known models species, locomotor proficiency muscular anatomy through MRI (both lower leg hip region) were evaluated B6.A‐ Dysf...
Duchenne muscular dystrophy (DMD) is a severe, progressive neuromuscular disorder caused by reading frame disrupting mutations in the DMD gene leading to absence of functional dystrophin. Antisense oligonucleotide (AON)-mediated exon skipping therapeutic approach aimed at restoring pre-mRNA level, allowing production internally truncated partly dystrophin proteins. AONs work sequence specific manner, which warrants generating humanized mouse models for preclinical tests. To address this, we...
Duchenne muscular dystrophy (DMD) is a severe childhood muscle disease primarily caused by the lack of functional dystrophin at fiber membranes. Multiple therapeutic approaches are currently in (pre)clinical development, aimed restoring expression (truncated) dystrophin. Key questions this phase relate to route drug administration, dose regimen, and levels required improve function. A series studies applying antisense oligonucleotides (AONs)
Ibuprofen, a nonsteroidal anti-inflammatory drug, and nitric oxide (NO) donors have been reported to reduce the severity of muscular dystrophies in mice associated with absence dystrophin or <i>α</i>-sarcoglycan, but their effects on that are dystrophic due dysferlin not examined. We tested ibuprofen, as well isosorbide dinitrate (ISDN), NO donor, learn whether used alone together they protect dysferlin-null muscle A/J from large strain injury (LSI) induced by series high lengthening...
CVN mouse, with APPSweDI mutations and crossed NOS2 knockout line, exhibits wide range of AD hallmarks including increased insoluble Aβ plaque formation, inflammation, tau phosphorylation, hippocampal neuronal death behavioral deficits. Validation data from Charles River mouse in-house testing colony shows reproducible defects, positions as one the most complete rodent model available. Wild-type mice were studied at 3, 6, 9 12 months age. Behavioral battery included various tests o pen...
According to previously published data and internal model validation, the CVN mouse of AD exhibits cognitive impairments in contextual fear conditioning, Barnes maze radial arm water most prominently at 9–12 months age. To determine if impaired learning can be detected an earlier age, we evaluated their performance by using a touch screen operant platform (Horner et al., 2013), which is similar computerized CANTAB testing widely used clinical setting. Cohorts 4–5-month old male (APPSDI/NOS2...
CVN mouse, with APPSweDI mutations and crossed NOS2 knockout line, exhibits wide range of AD hallmarks including increased insoluble Aβ plaque formation, inflammation, tau phosphorylation, hippocampal neuronal death behavioral deficits (Wilcock et al 2008). Validation data from Charles River mouse in-house testing colony shows reproducible defects, positions as the most complete model available. Wild-type mice were studied starting at age 3 months. Behavioral battery included Open field,...
Stroke is a major cause of disability in the elderly. In particular, cerebrovascular lesions may contribute to pathogenesis Alzheimer's disease (AD), as up 90 % patients show pathology at autopsy. Interestingly, several transgenic mouse models AD have shown increased vulnerability ischemia an early age. Because recent studies indicate that clinically safe intravenous immunoglobulin (IVIG) dose 2 g/kg provides protection against focal brain young wild-type (wt) mice, we investigated whether...