Research Topics
Genomes and Genes | ILYA B BEZPROZVANNYSummaryAffiliation: University of Texas Southwestern Medical Center Country: USA Publications
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Publications
Familial Alzheimer disease-linked mutations specifically disrupt Ca2+ leak function of presenilin 1Omar Nelson
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
J Clin Invest 117:1230-9. 2007..Our observations are consistent with the potential role of disturbed Ca(2+) homeostasis in Alzheimer disease pathogenesis...- Presenilins: a novel link between intracellular calcium signaling and lysosomal function?Ilya Bezprozvanny
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
J Cell Biol 198:7-10. 2012..Now, in this issue, Coen et al. (2012. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201201076) provide a series of results that challenge this idea and propose instead that presenilins play a role in calcium-mediated lysosomal fusion... - Calcium signaling and neurodegenerationI B Bezprozvanny
University of Texas Southwestern Medical Center
Acta Naturae 2:72-82. 2010..Based on the results we reviewed, we conclude that the calcium channels and other proteins involved in the neuronal calcium signaling system are potential drug targets for AD, PD, ALS, HD, and SCA therapy... - Acute dosing of latrepirdine (Dimebon), a possible Alzheimer therapeutic, elevates extracellular amyloid-beta levels in vitro and in vivoJohn W Steele
Departments of Neurology, Psychiatry and Alzheimer s Disease Research Center, Mount Sinai School of Medicine, New York, NY, 10029, USA
Mol Neurodegener 4:51. 2009..In the current study, we assessed the effect of acute dosing of latrepirdine on levels of extracellular Abeta using in vitro and in vivo experimental systems... - Tetrabenazine is neuroprotective in Huntington's disease miceHongyu Wang
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
Mol Neurodegener 5:18. 2010..TBZ acts by reducing dopaminergic input to the striatum... - Elucidating a normal function of huntingtin by functional and microarray analysis of huntingtin-null mouse embryonic fibroblastsHua Zhang
Department of Physiology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
BMC Neurosci 9:38. 2008..Therefore, in addition to elucidating the mechanisms responsible for polyQ-mediated pathology, it is also important to understand the normal function of Htt protein for both basic biology and for HD... 
The rise and fall of DimebonIlya Bezprozvanny
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA
Drug News Perspect 23:518-23. 2010..Careful preclinical studies of novel potential therapies are needed to minimize chances of making similar costly mistakes in the future...- Amyloid goes globalIlya Bezprozvanny
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
Sci Signal 2:pe16. 2009..These results have potential implications for understanding synaptic and neuronal network dysfunction in AD brains... - Role of inositol 1,4,5-trisphosphate receptors in pathogenesis of Huntington's disease and spinocerebellar ataxiasIlya Bezprozvanny
Department of Physiology, ND12 200AA, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390 9040, USA
Neurochem Res 36:1186-97. 2011..Based on these results I propose that IP(3)R and other Ca(2+) signaling proteins should be considered as potential therapeutic targets for treatment of HD and SCAs... - Calcium signaling and neurodegenerative diseasesIlya Bezprozvanny
Department of Physiology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390 9040, USA
Trends Mol Med 15:89-100. 2009..It is reasoned that Ca2+ blockers will be most beneficial clinically when used in combination with other disease-specific therapeutic approaches... - Neuronal calcium mishandling and the pathogenesis of Alzheimer's diseaseIlya Bezprozvanny
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Trends Neurosci 31:454-63. 2008..Emerging knowledge of the actions of Ca(2+) upstream and downstream of Abeta provides opportunities to develop novel preventative and therapeutic interventions for AD... 
Inositol 1,4,5-tripshosphate receptor, calcium signalling and Huntington's diseaseI Bezprozvanny
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
Subcell Biochem 45:323-35. 2007..These results indicate that InsP3R and other Ca2+ signaling proteins should be considered as potential therapeutic targets for treatment of HD...- Deranged neuronal calcium signaling and Huntington diseaseIlya Bezprozvanny
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
Biochem Biophys Res Commun 322:1310-7. 2004..Based on these results we propose that Httexp-induced cytosolic and mitochondrial Ca2+ overload of MSN plays an important role in the pathogenesis of HD and that Ca2+ signaling blockers may play a beneficial role in treatment of HD... - Evaluation of Dimebon in cellular model of Huntington's diseaseJun Wu
Department of Physiology, UT Southwestern Medical Center at Dallas, TX 75390, USA
Mol Neurodegener 3:15. 2008..It has been suggested that Dimebon may act by blocking NMDA receptors or voltage-gated Ca2+ channels and by preventing mitochondrial permeability pore transition... - Classification of PDZ domainsI Bezprozvanny
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75235 9040, USA
FEBS Lett 509:457-62. 2001..The proposed classification helps to organize PDZ domain containing proteins... - Dantrolene is neuroprotective in Huntington's disease transgenic mouse modelXi Chen
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
Mol Neurodegener 6:81. 2011..The aim of the current study was to evaluate potential beneficial effects of dantrolene in experiments with YAC128 HD mouse model... - Huntingtin and huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1,4,5) triphosphate receptor type 1Tie Shan Tang
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
Neuron 39:227-39. 2003..Our findings identify a novel molecular link between Htt and InsP3R1-mediated neuronal Ca2+ signaling and provide an explanation for the derangement of cytosolic Ca2+ signaling in HD patients and mouse models... - Full length mutant huntingtin is required for altered Ca2+ signaling and apoptosis of striatal neurons in the YAC mouse model of Huntington's diseaseHua Zhang
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
Neurobiol Dis 31:80-8. 2008..Furthermore, the results obtained with neurons from shortstop mice provide additional evidence that not all fragments of mutant Htt(exp) are toxic to neurons... - Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer's disease-linked mutationsHuiping Tu
Department of Physiology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
Cell 126:981-93. 2006..The ER Ca(2+) leak function of presenilins is independent of their gamma-secretase activity. Our data suggest a Ca(2+) signaling function for presenilins and provide support for the "Ca(2+) hypothesis of AD.".. - The dysregulation of intracellular calcium in Alzheimer diseaseCharlene Supnet
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390 9040, USA
Cell Calcium 47:183-9. 2010..Clearly, a better understanding of how dysregulation of neuronal Ca2+ handling contributes to neurodegeneration and neuroprotection in AD is needed as Ca2+ signalling modulators are targets of great interest as potential AD therapeutics... - Dopamine receptor-mediated Ca(2+) signaling in striatal medium spiny neuronsTie Shan Tang
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9040, USA
J Biol Chem 279:42082-94. 2004..Our results indicate that, following D1 class DAR activation, InsP(3) and cAMP signaling pathways converge on the type 1 InsP(3) receptor, resulting in Ca(2+) oscillations in MSN... - HAP1 facilitates effects of mutant huntingtin on inositol 1,4,5-trisphosphate-induced Ca release in primary culture of striatal medium spiny neuronsTie Shan Tang
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
Eur J Neurosci 20:1779-87. 2004..Our present results indicate that HAP1 plays an important role in functional interactions between Htt and InsP3R1... - Secondary structure of Huntingtin amino-terminal regionMee Whi Kim
Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
Structure 17:1205-12. 2009..We further propose that the pathogenic polyQ expansion in the Htt protein increases the length of the random coil, which promotes aggregation and facilitates abnormal interactions with other proteins in cells... - The inositol 1,4,5-trisphosphate receptorsIlya Bezprozvanny
University of Texas, Department of Physiology, UT Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, Texas 75390 9040, USA
Cell Calcium 38:261-72. 2005..The main focus is on the InsP3R1, but the recent information about properties of other InsP3R isoforms is also discussed... - G-protein-coupled receptor modulation of striatal CaV1.3 L-type Ca2+ channels is dependent on a Shank-binding domainPatricia A Olson
Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
J Neurosci 25:1050-62. 2005..Together, these results suggest that Shank promotes the assembly of a signaling complex at corticostriatal synapses that enables key GPCRs to regulate L-type Ca2+ channels and the integration of glutamatergic synaptic events... - Association of the type 1 inositol (1,4,5)-trisphosphate receptor with 4.1N protein in neuronsAnton Maximov
Department of Physiology, UT Southwestern Medical Center at Dallas, 75390, Dallas, TX, USA
Mol Cell Neurosci 22:271-83. 2003..1N-CASK-syndecan-2 quaternary complex formation. From our findings we hypothesize that InsP(3)R1-4.1N association may play a role in InsP(3)R1 localization or Ca(2+) signaling in neurons... - Neuroprotective effects of inositol 1,4,5-trisphosphate receptor C-terminal fragment in a Huntington's disease mouse modelTie Shan Tang
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
J Neurosci 29:1257-66. 2009..Our data also support potential use of IC10 peptide as a novel HD therapeutic agent... - Allele-specific silencing of mutant huntingtin and ataxin-3 genes by targeting expanded CAG repeats in mRNAsJiaxin Hu
Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA
Nat Biotechnol 27:478-84. 2009..Antisense oligomers that discriminate between wild-type and mutant genes on the basis of repeat length may offer new options for developing treatments for MJD, HD and related hereditary diseases... - The high-affinity calcium[bond]calmodulin-binding site does not play a role in the modulation of type 1 inositol 1,4,5-trisphosphate receptor function by calcium and calmodulinElena Nosyreva
Department of Physiology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390, U S A
Biochem J 365:659-67. 2002.... - Modulation of type 1 inositol (1,4,5)-trisphosphate receptor function by protein kinase a and protein phosphatase 1alphaTie-Shan Tang
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9040, USA
J Neurosci 23:403-15. 2003..Based on these data, we suggest that InsP3R1 may participate in cross talk between cAMP and Ca2+ signaling in the neostriatum and possibly in other regions of the brain... - Ca1.2 and CaV1.3 neuronal L-type calcium channels: differential targeting and signaling to pCREBHua Zhang
Department of Physiology, UT Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
Eur J Neurosci 23:2297-310. 2006..3 channels play a more important role in pCREB signaling in striatal medium spiny neurons than in hippocampal neurons. Our results provide novel insights into the function of CaV1.2 and CaV1.3 L-type Ca2+ channels in the brain... - Association of CaV1.3 L-type calcium channels with ShankHua Zhang
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
J Neurosci 25:1037-49. 2005..3 L-type Ca2+ channels in pCREB signaling... - Functional and biochemical analysis of the type 1 inositol (1,4,5)-trisphosphate receptor calcium sensorHuiping Tu
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9040, USA
Biophys J 85:290-9. 2003..2 micro M for the wild-type channels and 1-2 micro M Ca(2+) for the E2100D and E2100Q mutants. The results obtained in our study support the hypothesis that E2100 residue forms a part of the InsP(3)R1 Ca(2+) sensor... - Neuronal calcium signaling, mitochondrial dysfunction, and Alzheimer's diseaseCharlene Supnet
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA
J Alzheimers Dis 20:S487-98. 2010..We also discuss latest and planned AD therapeutic trials of agents targeting Ca2+ channels and mitochondria... - Small-molecule activation of neuronal cell fateJay W Schneider
Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA
Nat Chem Biol 4:408-10. 2008..These results provide new tools to explore the epigenetic signaling circuitry specifying neuronal cell fate and new leads for neuro-regenerative drugs... - Disturbed Ca2+ signaling and apoptosis of medium spiny neurons in Huntington's diseaseTie-Shan Tang
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Proc Natl Acad Sci U S A 102:2602-7. 2005..These findings also suggest that Ca2+ and MPTP blockers may have a therapeutic potential for treatment of HD... - Role of presenilins in neuronal calcium homeostasisHua Zhang
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
J Neurosci 30:8566-80. 2010..These results indicate that disruption of ER Ca(2+) leak function of presenilins may play an important role in AD pathogenesis... - Functional characterization of the type 1 inositol 1,4,5-trisphosphate receptor coupling domain SII(+/-) splice variants and the Opisthotonos mutant formHuiping Tu
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
Biophys J 82:1995-2004. 2002..24 mM); 5) the InsP3R1-SII(-) is approximately twofold more active than the InsP3R1-SII(+) in the absence of ATP. Obtained results provide novel information about the molecular determinants of the InsP3R1 function... - Reelin modulates NMDA receptor activity in cortical neuronsYing Chen
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
J Neurosci 25:8209-16. 2005..Thus, Reelin may physiologically modulate learning and memory by modulating NMDA receptor functions... - Deranged calcium signaling and neurodegeneration in spinocerebellar ataxia type 2Jing Liu
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
J Neurosci 29:9148-62. 2009..Results of our studies indicate that disturbed neuronal Ca(2+) signaling may play an important role in SCA2 pathology and also suggest that the RyanR constitutes a potential therapeutic target for treatment of SCA2 patients... - Functional properties of the Drosophila melanogaster inositol 1,4,5-trisphosphate receptor mutantsSonal Srikanth
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, USA
Biophys J 86:3634-46. 2004..Our study validates the use of D. melanogaster as an appropriate model for InsP(3)R structure-function studies and provides novel insights into the fundamental mechanisms of the InsP(3)R function... - Ginsenosides protect striatal neurons in a cellular model of Huntington's diseaseJun Wu
Department of Physiology, UT Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
J Neurosci Res 87:1904-12. 2009..From these results we concluded that ginsenosides Rb1, Rc, and Rg5 offer a potential therapeutic choice for the treatment of HD and possibly other neurodegenerative disorders... - Modulation of mammalian inositol 1,4,5-trisphosphate receptor isoforms by calcium: a role of calcium sensor regionHuiping Tu
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
Biophys J 88:1056-69. 2005..Obtained results provide novel information about functional properties of mammalian InsP3R isoforms and support the importance of the Ca2+ sensor region (Cas) in determining the sensitivity of InsP3R isoforms to modulation by Ca2+... - Association of type 1 inositol 1,4,5-trisphosphate receptor with AKAP9 (Yotiao) and protein kinase AHuiping Tu
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390 9040, USA
J Biol Chem 279:19375-82. 2004..The obtained results advance our understanding of cross-talk between cAMP and InsP(3)/Ca(2+) signaling pathways in the brain... - Deranged calcium signaling and neurodegeneration in spinocerebellar ataxia type 3Xi Chen
Department of Physiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
J Neurosci 28:12713-24. 2008..Our results indicate that deranged Ca(2+) signaling may play an important role in SCA3 pathology and that Ca(2+) signaling stabilizers such as dantrolene may be considered as potential therapeutic drugs for treatment of SCA3 patients... - The store-operated calcium entry pathways in human carcinoma A431 cells: functional properties and activation mechanismsKonstantin Gusev
Department of Physiology, K4.112, UT Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390-9040, USA
J Gen Physiol 122:81-94. 2003..Our findings provide novel information about store-operated Ca2+ influx pathways in A431 cells... - Evaluation of clinically relevant glutamate pathway inhibitors in in vitro model of Huntington's diseaseJun Wu
Department of Physiology, UT Southwestern Medical Center at Dallas, TX, USA
Neurosci Lett 407:219-23. 2006..Our results provide further support to potential use of memantine and riluzole for treatment of HD... - Synaptic targeting of N-type calcium channels in hippocampal neuronsAnton Maximov
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390 9040, USA
J Neurosci 22:6939-52. 2002..Our results provide a novel insight into the molecular mechanisms responsible for targeting of Ca2+ channels and other synaptic proteins in neurons... - Functional characterization of mammalian inositol 1,4,5-trisphosphate receptor isoformsHuiping Tu
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
Biophys J 88:1046-55. 2005..3); 7), ATP modulates InsP3R3 gating in a highly cooperative manner (n(Hill) = 4.1). Obtained results provide novel information about functional properties of mammalian InsP3R isoforms... - Dopaminergic signaling and striatal neurodegeneration in Huntington's diseaseTie Shan Tang
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390, USA
J Neurosci 27:7899-910. 2007....
Research Grants
- Deranged calcium signaling and polyglutamine expansion disordersILYA B BEZPROZVANNY; Fiscal Year: 2010..The experiments described in the grant are aimed at testing specific hypothesis regarding pathogenesis of these diseases and will provide information critical for development of the cure. ..
- Structure-function of inositol trisphosphate receptorIlya Bezprozvanny; Fiscal Year: 2009..Dopamine-induced responses in striatal medium spiny neurons will be studied by Ca2+ imaging. Experiments with striatal neurons from DARPP-32 and D2 receptor knockout mice will be performed. ..
- Presenilins and neuronal calcium signalingILYA B BEZPROZVANNY; Fiscal Year: 2010..These data will also help to evaluate "Ca2+ hypothesis of AD" and will contribute to selecting optimal strategies for treatment of AD. ..
- STRUCTURE/FUNCTION OF INOSITOL TRISPHOSPHATE RECEPTORIlya Bezprozvanny; Fiscal Year: 2002..Activity of InsP3R will be correlated with cellular PIP2 content to obtain information regarding InsP3R-PIP2 interaction in situ. ..
- INTERACTIONS OF CALCIUM CHANNELS WITH ADAPTOR PROTEINSIlya Bezprozvanny; Fiscal Year: 2003....
- Screen:Blockers of a CaV2.2-Mint-PDZ1 association (RMI)Ilya Bezprozvanny; Fiscal Year: 2004..Biological activity of compounds identified in the full HTS screen will be tested in whole animal pain assays (formalin, hot plate, tail flick). ..
- Deranged calcium signaling and polyglutamine expansion disordersILYA B BEZPROZVANNY; Fiscal Year: 2011..The experiments described in the grant are aimed at testing specific hypothesis regarding pathogenesis of these diseases and will provide information critical for development of the cure. ..