Alterations in the ryanodine receptor calcium release channel correlate with Alzheimer's disease neurofibrillary and β-amyloid pathologies

Kelliher, Mary; Fastbom, Johan; Cowburn, Richard F.; Bonkale, Willy L.; Ohm, Thomas G.; Ravid, Rivka; Sorrentino, Vincenzo; O’Neill, Cora

doi:10.1016/s0306-4522(99)00042-1

Cited by 139 publications

(123 citation statements)

References 80 publications

Supporting

Mentioning

115

Contrasting

Order By: Relevance

“…The activation of these enzymes destroys the cellular skeleton and membrane lipid, leading to the formation of arachidonic acid metabolic products, free radicals and mitochondrial function obstruction. a serious case may result in energy exhaustion and cell death, in which ca 2+ plays a key role in the mechanism of damage caused by glutamic acid nervous excitatory toxicity (15). in addition, by increasing ca 2+ , nMda receptor activation may activate noS and produce no.…”

Section: Discussion Dynamic Changes In Camentioning

confidence: 99%

Effects of infrasound at 8ï¿½Hz 90ï¿½dB/130ï¿½dB on NMDAR1 expression and changes in intracellular calcium ion concentration in the hippocampus of rats

et al. 2010

View full text Add to dashboard Cite

Abstract. in the present study, we investigated the effect of infrasound on the expression of n-methyl-d-aspartate (nMdar)1 as well as changes in intracellular calcium ion concentration ([ca 2+ ] i ) in the hippocampus of rats. Spraguedawley (Sd) rats were exposed for 2 h daily to infrasound at 8 Hz 90 dB or 130 dB, and nMdar1 expression was examined on days 1, 7, 14, 21 and 28. The expression of nMdar1 in the rat hippocampus upon exposure to infrasound at 8 Hz 90 dB sound pressure level (SPl) showed an initial decrease on day 1, an increase on days 7 and 14, a further decrease on day 21, and a return to normal levels on day 28. The peak level was observed on day 14 in every examined subregion of the hippocampus. By contrast, exposure to infrasound at 8 Hz 130 dB SPl had opposite effects, showing an increase on day 1, a decrease on day 7, a decrease to the lowest point on days 14, another increase on day 21 and a return to normal levels on day 28. The lowest expression of nMdar1 was found in the ca1 and ca3 regions on day 14 and in the dG region on day 7 with exposure at 130 dB. There were significant differences in [

show abstract

Section: Discussion Dynamic Changes In Camentioning

confidence: 99%

Effects of infrasound at 8ï¿½Hz 90ï¿½dB/130ï¿½dB on NMDAR1 expression and changes in intracellular calcium ion concentration in the hippocampus of rats

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Human brain tissue fractions from the mid-temporal cortex were prepared as previously described [32], using conditions that were compatible with measuring both b-secretase activity, and detection of BACE1/BACE2 by western immunoblot analysis. Briefly, frozen brain tissue was thawed rapidly at 37°C in homogenisation buffer [20 mM PIPES-KOH (pH 7.4), 0.32 M sucrose, 1 lg/ml leupeptin, 1 lg/ml aprotinin, 1 lg/ml pepstatin and 0.5 mM phenylmethylsulphonyl fluoride (PMSF)].…”

Section: Preparation Of Tissue Fractionsmentioning

confidence: 99%

Altered β‐secretase enzyme kinetics and levels of both BACE1 and BACE2 in the Alzheimer's disease brain

2006

View full text Add to dashboard Cite

b-Secretase is the rate limiting enzymatic activity in the production of amyloid-b peptide, the primary component of senile plaque pathology in Alzheimer's disease (AD). This study performed the first comparative analysis of b-secretase enzyme kinetics in AD and control brain tissue. Results found V max values for b-secretase to be significantly increased, and K m values unchanged in AD temporal cortex compared to matched control temporal cortex. The increased V max in AD cases, did not correlate with levels of BACE1, and decreased BACE1 and BACE2 levels correlated with the severity of neurofibrillary pathology (I-VI), and synaptic loss in AD. These results indicate that increased V max for b-secretase is a feature of AD pathogenesis and this increase does not correlate directly with levels of BACE1, the principal b-secretase in brain.

show abstract

“…We recently showed that alterations in the functioning of RyR2 are contributing causes for the development of a diabetic cardiomyopathy (Shao et al, 2012). Others have also identified changes in function of RyRs in Alzheimer's disease (Kelliher et al, 1999) and myasthenia gravis (Skeie et al, 2003).…”

Section: A Transient Rise In Intracellular Camentioning

confidence: 99%

CCDI: a new ligand that modulates mammalian type 1 ryanodine receptor (RyR1)

Tian

Shao

Padanilam

et al. 2014

British J Pharmacology

View full text Add to dashboard Cite

BACKGROUND AND PURPOSERyanodine receptors (RyRs) are Ca 2+ -release channels on the sarco(endo)plasmic reticulum that modulate a wide array of physiological functions. Three RyR isoforms are present in cells: RyR1, RyR2 and RyR3. To date, there are no reports on ligands that modulate RyR in an isoform-selective manner. Such ligands are not only valuable research tools, but could serve as intermediates for development of therapeutics. EXPERIMENTAL APPROACHPyrrole-2-carboxylic acid and 1,3-dicyclohexylcarbodiimide were allowed to react in carbon tetrachloride for 24 h at low temperatures and pressures. The chemical structures of the two products isolated were elucidated using NMR spectrometry, mass spectrometry and elemental analyses. KEY RESULTSThe major product, 2-cyclohexyl-3-cyclohexylimino-2, 3, dihydro-pyrrolo[1,2-c]imidazol-1-one (CCDI) dose-dependently potentiated Ca CONCLUSIONS AND IMPLICATIONSA new ligand that preferentially modulates RyR1 was identified. In addition to being an important research tool, the pharmacophore of this small molecule could serve as a template for the synthesis of other isoform-selective modulators of RyRs. Abbreviations

show abstract

Alterations in the ryanodine receptor calcium release channel correlate with Alzheimer's disease neurofibrillary and β-amyloid pathologies

Cited by 139 publications

References 80 publications

Effects of infrasound at 8ï¿½Hz 90ï¿½dB/130ï¿½dB on NMDAR1 expression and changes in intracellular calcium ion concentration in the hippocampus of rats

Effects of infrasound at 8ï¿½Hz 90ï¿½dB/130ï¿½dB on NMDAR1 expression and changes in intracellular calcium ion concentration in the hippocampus of rats

Altered β‐secretase enzyme kinetics and levels of both BACE1 and BACE2 in the Alzheimer's disease brain

CCDI: a new ligand that modulates mammalian type 1 ryanodine receptor (RyR1)

Contact Info

Product

Resources

About