A5070193958- Neuroscience and Neuropharmacology Research
- Autophagy in Disease and Therapy
- Genetic and Kidney Cyst Diseases
- Biomedical Research and Pathophysiology
- Ion channel regulation and function
- Memory and Neural Mechanisms
- Renal and related cancers
- Renal cell carcinoma treatment
- Protein Kinase Regulation and GTPase Signaling
- Acute Kidney Injury Research
- Chemotherapy-induced organ toxicity mitigation
- Photoreceptor and optogenetics research
- Cell death mechanisms and regulation
- RNA modifications and cancer
- Dietary Effects on Health
- Cannabis and Cannabinoid Research
- RNA Research and Splicing
- Alzheimer's disease research and treatments
- Nicotinic Acetylcholine Receptors Study
- Retinal Development and Disorders
- Genetic Syndromes and Imprinting
- Lipid metabolism and biosynthesis
- Pancreatic function and diabetes
- Dialysis and Renal Disease Management
- Receptor Mechanisms and Signaling
University of Colorado Anschutz Medical Campus
2020-2025
University of Colorado Denver
2017-2021
Learning and memory are thought to require hippocampal long-term potentiation (LTP), one of the few central dogmas molecular neuroscience that has stood undisputed for more than three decades is LTP induction requires enzymatic activity Ca
Advanced tumours may have met their match with new drugs, but why these treatments proved ineffective at stopping early-stage from coming back?
The Ca2+/calmodulin (CaM)-dependent protein kinase II (CaMKII) mediates physiological long-term potentiation (LTP) of synaptic strength and pathological ischemic neuronal cell death. Both functions require CaMKII autophosphorylation at T286 (pT286) binding to the NMDA-type glutamate receptor subunit GluN2B. neuroprotection seen with 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) was thought be mediated by impairing brain-specific CaMKIIα isozyme However, we show that HOCPCA does not...
Amyloid β (Aβ) inhibits hippocampal long-term potentiation (LTP; a form of synaptic plasticity thought to underly learning and memory) by inhibiting the stimulation-induced accumulation Ca 2+ /calmodulin (CaM)-dependent protein kinase II (CaMKII). Notably, CaMKII inhibition rescues both movement LTP, indicating that mediates LTP Aβ-induced impairment. Somewhat counterintuitively, we found here overexpression GFP-CaMKII also rescued impairment movement. For endogenous CaMKII, confirmed Aβ...
Autosomal dominant polycystic kidney disease (PKD) is characterized by cyst formation and growth, which are partially driven abnormal proliferation of tubular cells. Proproliferative mechanistic target rapamycin (mTOR) complexes 1 2 (mTORC1 mTORC2) activated in the kidneys mice with PKD. Sirolimus indirectly inhibits mTORC1. Novel mTOR kinase inhibitors directly inhibit kinase, resulting inhibition mTORC1 mTORC2. The aim present study was to determine effects sirolimus versus inhibitor...
The Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a central regulator of learning and memory, which poses problem for targeting it therapeutically. Indeed, our study supports prior conclusions that long-term interference with CaMKII signaling can erase pre-formed memories. By contrast, short-term pharmacological inhibition the neuroprotective peptide tatCN19o interfered in mice only mildly transiently (for less than 1 h) did not at all reverse These results were obtained ≥500-fold...
Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary renal disease, characterized by cyst formation and growth. Hyperproliferation a major contributor to At nexus of regulating proliferation, 4E-BP1. We demonstrate that ADPKD mouse rat models, patient biopsies PKD1-/- cells exhibited hyperphosphorylated 4E-BP1, biomarker increased translation proliferation. hypothesized expression constitutively active 4E-BP1 constructs (4E-BP1F113A 4E-BP1R13AF113A) would...
CaMKII is an important mediator of forms synaptic plasticity that are thought to underly learning and memory. The mutants K42M K42R have been used interchangeably as research tools, although some reported phenotypic differences suggest they may differ in the extent which impair ATP binding. Here, we directly compared two mutations at high concentrations exist within cells (~4 mM). We found both equally blocked GluA1 phosphorylation vitro GluN2B binding cells. Both also reduced but did not...
The Ca2+/Calmodulin-dependent protein kinase II (CaMKII) is a central regulator of synaptic plasticity and has been implicated in various neurological conditions, including schizophrenia. Here, we characterize six different CaMKIIα variants found patients with Only R396stop disrupted the 12-meric holoenzyme structure, GluN2B binding, localization. Additionally, impaired T286 autophosphorylation that generates Ca2+-independent "autonomous" activity. This impairment was shared by R8H mutation,...
The effect of IL-33 deficiency on acute kidney injury (AKI) and cancer growth in a 4-wk model cisplatin-induced AKI mice with was determined. Mice were injected subcutaneously murine lung cells. Ten days later, cisplatin (10 mg·kg-¹·wk-¹) administered weekly for 4 wk. increase preceded the tubular injury, suggesting that may play causative role. However, serum creatinine, blood urea nitrogen, neutrophil gelatinase-associated lipoprotein, necrosis, apoptosis scores same wild-type...
Abstract Many surgical models are used to study kidney and other diseases in mice, yet the effects of procedure itself on tissues have not been elucidated. In present study, we found that both sham surgery unilateral nephrectomy (UNX), which is as a model renal compensatory hypertrophy, mice resulted increased mammalian target rapamycin complex 1/2 (mTORC1/2) remaining kidney. mTORC1 known regulate lysosomal biogenesis autophagy. Genes associated with function were decreased UNX kidneys....
Aβ bears homology to the CaMKII regulatory domain, and peptides derived from this domain can bind disrupt holoenzyme, suggesting that could have a similar effect. Notably, impairs synaptic accumulation is mediated by GluN2B binding, which requires assembly into holoenzymes. Furthermore, Aβ-induced impairment prevented inhibitors should also inhibit putative direct binding. However, our study did not find any evidence for effects of on CaMKII: directly holoenzymes, T286 autophosphorylation,...
ABSTRACT The Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) is a central regulator of learning and memory, which poses problem for targeting it therapeutically. Indeed, our study supports prior conclusions that long-term interference with CaMKII signaling can erase pre-formed memories. By contrast, short-term pharmacological inhibition tatCN19o interfered in mice only mildly transiently (for less than 1 h) did not at all reverse This was ≥500fold the dose protected hippocampal...
Brown, Carolyn N.; Atwood, Daniel; Pokhrel, Deepak; Altmann, Chris; Faubel, Sarah; Edelstein, Charles L. Author Information
Atwood, Daniel; Pokhrel, Deepak; Brown, Carolyn N.; Hopp, Katharina; Edelstein, Charles L. Author Information
Atwood, Daniel; Brown, Carolyn N.; Hopp, Katharina; Edelstein, Charles L. Author Information