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Article ; Online: Upregulated Ca

Adeoye, Temitope / Shah, Syed I / Demuro, Angelo / Rabson, David A / Ullah, Ghanim

2022 Volume 11, Issue 14

Abstract: Neurotransmitter release from presynaptic terminals is primarily regulated by rapid ... ...

Abstract	Neurotransmitter release from presynaptic terminals is primarily regulated by rapid Ca
MeSH term(s)	Animals ; Alzheimer Disease/metabolism ; Calcium/metabolism ; Endoplasmic Reticulum/metabolism ; Neurotransmitter Agents/metabolism
Chemical Substances	Calcium (SY7Q814VUP) ; Neurotransmitter Agents
Language	English
Publishing date	2022-07-11
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11142167
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Intracellular Injection of Brain Extracts from Alzheimer's Disease Patients Triggers Unregulated Ca

Pensalfini, Anna / Umar, Abdul Rahim / Glabe, Charles / Parker, Ian / Ullah, Ghanim / Demuro, Angelo

Cells

2022 Volume 11, Issue 22

Abstract: Strong evidence indicates that amyloid beta (Aβ) inflicts its toxicity in Alzheimer's disease (AD) by promoting uncontrolled elevation of cytosolic ... ...

Abstract	Strong evidence indicates that amyloid beta (Aβ) inflicts its toxicity in Alzheimer's disease (AD) by promoting uncontrolled elevation of cytosolic Ca
MeSH term(s)	Humans ; Alzheimer Disease ; Amyloid beta-Peptides/metabolism ; Calcium/metabolism ; Brain/metabolism ; Energy Metabolism
Chemical Substances	Amyloid beta-Peptides ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2022-11-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11223630
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Extracellular ATP Neurotransmission and Nicotine Sex-Specifically Modulate Habenular Neuronal Activity in Adolescence.

Chen, Yen-Chu / Rindner, Daniel Jun / Fowler, James P / Lallai, Valeria / Mogul, Allison / Demuro, Angelo / Lur, Gyorgy / Fowler, Christie D

The Journal of neuroscience : the official journal of the Society for Neuroscience

2023 Volume 43, Issue 48, Page(s) 8259–8270

Abstract: The recent increase in the use of nicotine products by teenagers has revealed an urgent need to better understand the impact of nicotine on the adolescent brain. Here, we sought to examine the actions of extracellular ATP as a neurotransmitter and to ... ...

Abstract	The recent increase in the use of nicotine products by teenagers has revealed an urgent need to better understand the impact of nicotine on the adolescent brain. Here, we sought to examine the actions of extracellular ATP as a neurotransmitter and to investigate whether ATP and nicotinic signaling interact during adolescence. With the GRAB
MeSH term(s)	Male ; Adolescent ; Female ; Humans ; Nicotine/pharmacology ; Nicotinic Agonists/pharmacology ; Habenula ; Electronic Nicotine Delivery Systems ; Synaptic Transmission ; Cholinergic Neurons ; Receptors, Purinergic P2/physiology ; Adenosine Triphosphate/pharmacology
Chemical Substances	Nicotine (6M3C89ZY6R) ; Nicotinic Agonists ; Receptors, Purinergic P2 ; Adenosine Triphosphate (8L70Q75FXE)
Language	English
Publishing date	2023-11-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.1290-23.2023
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Article ; Online: Quantifying the dose-dependent impact of intracellular amyloid beta in a mathematical model of calcium regulation in xenopus oocyte.

Minicucci, Joseph / Alfond, Molly / Demuro, Angelo / Gerberry, David / Latulippe, Joe

PloS one

2021 Volume 16, Issue 1, Page(s) e0246116

Abstract: Alzheimer's disease (AD) is a devastating illness affecting over 40 million people worldwide. Intraneuronal rise of amyloid beta in its oligomeric forms (iAβOs), has been linked to the pathogenesis of AD by disrupting cytosolic Ca2+ homeostasis. However, ...

Abstract	Alzheimer's disease (AD) is a devastating illness affecting over 40 million people worldwide. Intraneuronal rise of amyloid beta in its oligomeric forms (iAβOs), has been linked to the pathogenesis of AD by disrupting cytosolic Ca2+ homeostasis. However, the specific mechanisms of action are still under debate and intense effort is ongoing to improve our understanding of the crucial steps involved in the mechanisms of AβOs toxicity. We report the development of a mathematical model describing a proposed mechanism by which stimulation of Phospholipase C (PLC) by iAβO, triggers production of IP3 with consequent abnormal release of Ca2+ from the endoplasmic reticulum (ER) through activation of IP3 receptor (IP3R) Ca2+ channels. After validating the model using experimental data, we quantify the effects of intracellular rise in iAβOs on model solutions. Our model validates a dose-dependent influence of iAβOs on IP3-mediated Ca2+ signaling. We investigate Ca2+ signaling patterns for small and large iAβOs doses and study the role of various parameters on Ca2+ signals. Uncertainty quantification and partial rank correlation coefficients are used to better understand how the model behaves under various parameter regimes. Our model predicts that iAβO alter IP3R sensitivity to IP3 for large doses. Our analysis also shows that the upstream production of IP3 can influence Aβ-driven solution patterns in a dose-dependent manner. Model results illustrate and confirm the detrimental impact of iAβOs on IP3 signaling.
MeSH term(s)	Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; Animals ; Calcium/metabolism ; Calcium Signaling ; Humans ; Models, Biological ; Oocytes/metabolism ; Xenopus ; Xenopus Proteins/metabolism
Chemical Substances	Amyloid beta-Peptides ; Xenopus Proteins ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2021-01-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0246116
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Quantifying the dose-dependent impact of intracellular amyloid beta in a mathematical model of calcium regulation in xenopus oocyte.

Joseph Minicucci / Molly Alfond / Angelo Demuro / David Gerberry / Joe Latulippe

PLoS ONE, Vol 16, Iss 1, p e

2021 Volume 0246116

Abstract	Alzheimer's disease (AD) is a devastating illness affecting over 40 million people worldwide. Intraneuronal rise of amyloid beta in its oligomeric forms (iAβOs), has been linked to the pathogenesis of AD by disrupting cytosolic Ca2+ homeostasis. However, the specific mechanisms of action are still under debate and intense effort is ongoing to improve our understanding of the crucial steps involved in the mechanisms of AβOs toxicity. We report the development of a mathematical model describing a proposed mechanism by which stimulation of Phospholipase C (PLC) by iAβO, triggers production of IP3 with consequent abnormal release of Ca2+ from the endoplasmic reticulum (ER) through activation of IP3 receptor (IP3R) Ca2+ channels. After validating the model using experimental data, we quantify the effects of intracellular rise in iAβOs on model solutions. Our model validates a dose-dependent influence of iAβOs on IP3-mediated Ca2+ signaling. We investigate Ca2+ signaling patterns for small and large iAβOs doses and study the role of various parameters on Ca2+ signals. Uncertainty quantification and partial rank correlation coefficients are used to better understand how the model behaves under various parameter regimes. Our model predicts that iAβO alter IP3R sensitivity to IP3 for large doses. Our analysis also shows that the upstream production of IP3 can influence Aβ-driven solution patterns in a dose-dependent manner. Model results illustrate and confirm the detrimental impact of iAβOs on IP3 signaling.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: PunctaSpecks: A tool for automated detection, tracking, and analysis of multiple types of fluorescently labeled biomolecules.

Shah, Syed Islamuddin / Ong, Hwei Ling / Demuro, Angelo / Ullah, Ghanim

Cell calcium

2020 Volume 89, Page(s) 102224

Abstract: Recent advances in imaging technology and fluorescent probes have made it possible to gain information about the dynamics of subcellular processes at unprecedented spatiotemporal scales. Unfortunately, a lack of automated tools to efficiently process the ...

Abstract	Recent advances in imaging technology and fluorescent probes have made it possible to gain information about the dynamics of subcellular processes at unprecedented spatiotemporal scales. Unfortunately, a lack of automated tools to efficiently process the resulting imaging data encoding fine details of the biological processes remains a major bottleneck in utilizing the full potential of these powerful experimental techniques. Here we present a computational tool, called PunctaSpecks, that can characterize fluorescence signals arising from a wide range of biological molecules under normal and pathological conditions. Among other things, the program can calculate the number, areas, life-times, and amplitudes of fluorescence signals arising from multiple sources, track diffusing fluorescence sources like moving mitochondria, and determine the overlap probability of two processes or organelles imaged using indicator dyes of different colors. We have tested PunctaSpecks on synthetic time-lapse movies containing mobile fluorescence objects of various sizes, mimicking the activity of biomolecules. The robustness of the software is tested by varying the level of noise along with random but known pattern of appearing, disappearing, and movement of these objects. Next, we use PunctaSpecks to characterize protein-protein interaction involved in store-operated Ca
MeSH term(s)	Algorithms ; Amyloid beta-Peptides/metabolism ; Automation ; Calcium/metabolism ; Calcium Signaling/drug effects ; Cell Membrane/drug effects ; Cell Membrane/metabolism ; Cerebral Cortex/cytology ; Diffusion ; Fluorescent Dyes/chemistry ; HEK293 Cells ; Humans ; Inositol 1,4,5-Trisphosphate/pharmacology ; Kinetics ; Neurons/drug effects ; Neurons/metabolism ; ORAI1 Protein/metabolism ; Software ; Stromal Interaction Molecule 1/metabolism
Chemical Substances	Amyloid beta-Peptides ; Fluorescent Dyes ; ORAI1 Protein ; Stromal Interaction Molecule 1 ; Inositol 1,4,5-Trisphosphate (85166-31-0) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2020-05-25
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	757687-0
ISSN	1532-1991 ; 0143-4160
ISSN (online)	1532-1991
ISSN	0143-4160
DOI	10.1016/j.ceca.2020.102224
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Zs.A 1596: Show issues

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Article ; Online: Noise analysis of cytosolic calcium image data.

Swaminathan, Divya / Dickinson, George D / Demuro, Angelo / Parker, Ian

Cell calcium

2019 Volume 86, Page(s) 102152

Abstract: ... Cellular ... ...

Abstract	Cellular Ca
MeSH term(s)	Animals ; Calcium/metabolism ; Calcium Channels/metabolism ; Catalytic Domain ; Cell Line, Tumor ; Cytosol/metabolism ; Fluorescence ; Humans ; Imaging, Three-Dimensional ; Inositol 1,4,5-Trisphosphate Receptors/metabolism ; Kinetics ; Xenopus
Chemical Substances	Calcium Channels ; Inositol 1,4,5-Trisphosphate Receptors ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2019-12-18
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	757687-0
ISSN	1532-1991 ; 0143-4160
ISSN (online)	1532-1991
ISSN	0143-4160
DOI	10.1016/j.ceca.2019.102152
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Picomolar sensitivity to inositol trisphosphate in Xenopus oocytes.

Demuro, Angelo / Parker, Ian

Cell calcium

2015 Volume 58, Issue 5, Page(s) 511–517

Abstract: Ca(2+) liberation from the endoplasmic reticulum mediated by inositol trisphosphate receptor/channels (IP3Rs) in response to production of the second messenger IP3 regulates numerous signaling pathways. However, estimates of resting and physiologically ... ...

Abstract	Ca(2+) liberation from the endoplasmic reticulum mediated by inositol trisphosphate receptor/channels (IP3Rs) in response to production of the second messenger IP3 regulates numerous signaling pathways. However, estimates of resting and physiologically relevant cytosolic concentrations of IP3 vary appreciably. Here we directly address this question, taking advantage of the large size of Xenopus oocytes to image Ca(2+) liberation evoked by bolus intracellular injections of known concentrations of IP3. Our principal finding is that IP3 evokes both global and local Ca(2+) signals in freshly isolated oocytes at concentrations as low as a few pM. A corollary is that basal, resting [IP3] must be even lower, given the absence of detectable Ca(2+) signals before injection. The dose/response curve for IP3-activation of Ca(2+) liberation suggests that freshly isolated oocytes express two distinct functional populations of IP3 receptors with EC50 values around 200 pM and tens of nM, whereas the high-affinity receptors are not apparent in oocytes examined later than about 3 days after isolation from the ovary.
MeSH term(s)	Animals ; Calcium/metabolism ; Calcium Signaling ; Inositol 1,4,5-Trisphosphate/analysis ; Inositol 1,4,5-Trisphosphate/metabolism ; Oocytes/metabolism ; Xenopus laevis
Chemical Substances	Inositol 1,4,5-Trisphosphate (85166-31-0) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2015-11
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	757687-0
ISSN	1532-1991 ; 0143-4160
ISSN (online)	1532-1991
ISSN	0143-4160
DOI	10.1016/j.ceca.2015.08.003
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Data-driven modeling of mitochondrial dysfunction in Alzheimer's disease.

Toglia, Patrick / Demuro, Angelo / Mak, Don-On Daniel / Ullah, Ghanim

Cell calcium

2018 Volume 76, Page(s) 23–35

Abstract: Intracellular accumulation of oligomeric forms of β amyloid (Aβ) are now believed to play a key role in the earliest phase of Alzheimer's disease (AD) as their rise correlates well with the early symptoms of the disease. Extensive evidence points to ... ...

Abstract	Intracellular accumulation of oligomeric forms of β amyloid (Aβ) are now believed to play a key role in the earliest phase of Alzheimer's disease (AD) as their rise correlates well with the early symptoms of the disease. Extensive evidence points to impaired neuronal Ca
MeSH term(s)	Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/metabolism ; Animals ; Calcium/metabolism ; Data Analysis ; Inositol 1,4,5-Trisphosphate Receptors/metabolism ; Mitochondria/metabolism ; Mitochondria/pathology ; Models, Biological ; Optical Imaging ; Patch-Clamp Techniques ; Xenopus laevis
Chemical Substances	Amyloid beta-Peptides ; Inositol 1,4,5-Trisphosphate Receptors ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2018-09-12
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	757687-0
ISSN	1532-1991 ; 0143-4160
ISSN (online)	1532-1991
ISSN	0143-4160
DOI	10.1016/j.ceca.2018.09.003
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Cytotoxicity of intracellular aβ42 amyloid oligomers involves Ca2+ release from the endoplasmic reticulum by stimulated production of inositol trisphosphate.

Demuro, Angelo / Parker, Ian

The Journal of neuroscience : the official journal of the Society for Neuroscience

2013 Volume 33, Issue 9, Page(s) 3824–3833

Abstract: Oligomeric forms of β-amyloid (Aβ(42)) peptides associated with Alzheimer's disease (AD) disrupt cellular Ca(2+) regulation by liberating Ca(2+) into the cytosol from both extracellular and intracellular sources. We elucidated the actions of ... ...

Abstract	Oligomeric forms of β-amyloid (Aβ(42)) peptides associated with Alzheimer's disease (AD) disrupt cellular Ca(2+) regulation by liberating Ca(2+) into the cytosol from both extracellular and intracellular sources. We elucidated the actions of intracellular Aβ by imaging Ca(2+) responses to injections of Aβ oligomers into Xenopus oocytes. Two types of signal were observed: (1) local, "channel-like" transients dependent on extracellular Ca(2+) influx, which resembled signals from amlyoid pores formed by extracellular application of oligomers; and (2) local transients and global Ca(2+) waves, resembling Ca(2+) puffs and waves mediated by inositol trisphosphate (IP(3)). The latter responses were suppressed by antagonists of the IP(3) receptor (caffeine and heparin), pretreatment with the G(i)(o)-protein inhibitor pertussis toxin, and pretreatment with lithium to deplete membrane inositol lipids. We show that G-protein-mediated stimulation of IP(3) production and consequent liberation of Ca(2+) from the endoplasmic reticulum by intracellular Aβ oligomers is cytotoxic, potentially representing a novel pathological mechanism in AD which may be further exacerbated by AD-linked mutations in presenilins to promote opening of IP(3) receptor/channels.
MeSH term(s)	Amyloid beta-Peptides/chemistry ; Animals ; Caffeine/pharmacology ; Calcium/metabolism ; Calcium Signaling/drug effects ; Cytosol/drug effects ; Cytosol/metabolism ; Dose-Response Relationship, Drug ; Endoplasmic Reticulum/drug effects ; Endoplasmic Reticulum/metabolism ; Extracellular Fluid/drug effects ; Extracellular Fluid/metabolism ; Heparin/pharmacology ; Humans ; Inositol 1,4,5-Trisphosphate/metabolism ; Inositol 1,4,5-Trisphosphate/pharmacology ; Membrane Potentials/drug effects ; Microinjections ; Oocytes/drug effects ; Oocytes/physiology ; Oocytes/ultrastructure ; Peptide Fragments/chemistry ; Peptides/pharmacology ; Pertussis Toxin/pharmacology ; Phosphodiesterase Inhibitors/pharmacology ; Xenopus laevis
Chemical Substances	Amyloid beta-Peptides ; Peptide Fragments ; Peptides ; Phosphodiesterase Inhibitors ; amyloid beta-protein (1-42) ; Caffeine (3G6A5W338E) ; Inositol 1,4,5-Trisphosphate (85166-31-0) ; Heparin (9005-49-6) ; Pertussis Toxin (EC 2.4.2.31) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2013-02-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.4367-12.2013
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