Regulation of the intracellular free calcium concentration in single rat dorsal root ganglion neurones in vitro.

Thayer, Stanley A.; Miller, Richard J.

doi:10.1113/jphysiol.1990.sp018094

Cited by 392 publications

(337 citation statements)

References 53 publications

(90 reference statements)

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“…Exacerbated activation of glutamate receptor-coupled calcium channels and subsequent increase in intracellular calcium concentrations ([Ca 2+ ] i ), followed by sustained disturbances in the [Ca 2+ ] i homeostasis, are established hallmarks of neuronal cell death in acute and chronic neurological diseases (29,30). Interestingly, activation of potassium intermediate/small conductance calciumactivated channel K Ca 2 prevented [Ca 2+ ] i deregulation and reduced neuronal death following glutamate toxicity and cerebral ischemia (31).…”

Section: Resultsmentioning

confidence: 99%

Essential protective role of tumor necrosis factor receptor 2 in neurodegeneration

Dong

Fischer

Naudé

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

137

158

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Despite the recognized role of tumor necrosis factor (TNF) in inflammation and neuronal degeneration, anti-TNF therapeutics failed to treat neurodegenerative diseases. Animal disease models had revealed the antithetic effects of the two TNF receptors (TNFR) in the central nervous system, whereby TNFR1 has been associated with inflammatory degeneration and TNFR2 with neuroprotection. We here show the therapeutic potential of selective inhibition of TNFR1 and activation of TNFR2 by ATROSAB, a TNFR1-selective antagonistic antibody, and EHD2-scTNF R2 , an agonistic TNFR2-selective TNF, respectively, in a mouse model of NMDA-induced acute neurodegeneration. Coadministration of either ATROSAB or EHD2-scTNF R2 into the magnocellular nucleus basalis significantly protected cholinergic neurons and their cortical projections against cell death, and reverted the neurodegeneration-associated memory impairment in a passive avoidance paradigm. Simultaneous blocking of TNFR1 and TNFR2 signaling, however, abrogated the therapeutic effect. Our results uncover an essential role of TNFR2 in neuroprotection. Accordingly, the therapeutic activity of ATROSAB is mediated by shifting the balance of the antithetic activity of endogenous TNF toward TNFR2, which appears essential for neuroprotection. Our data also explain earlier results showing that complete blocking of TNF activity by anti-TNF drugs was detrimental rather than protective and argue for the use of next-generation TNFR-selective TNF therapeutics as an effective approach in treating neurodegenerative diseases.

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Section: Resultsmentioning

confidence: 99%

Essential protective role of tumor necrosis factor receptor 2 in neurodegeneration

Dong

Fischer

Naudé

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

137

158

View full text Add to dashboard Cite

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“…Previous research has demonstrated mitochondrial site specificity for CCCP (Thayer and Miller, 1990;Friel and Tsien, 1994;Buttgereit and Brand, 1995;Park et al, 1996). Because the intramitochondrial calcium concentration is usually larger than that in the cytosol, CCCP application causes a transient increase in cytosolic calcium and a decrease in mitochondrial calcium (Biscoe et al, 1989;Simpson and Russell, 1996).…”

Section: Discussionmentioning

confidence: 99%

Calcium Homeostasis and Reactive Oxygen Species Production in Cells Transformed by Mitochondria from Individuals with Sporadic Alzheimer’s Disease

Sheehan

Swerdlow

Miller³

et al. 1997

J. Neurosci.

242

140

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Alzheimer's disease (AD) is associated with defects in mitochondrial function. Mitochondrial-based disturbances in calcium homeostasis, reactive oxygen species (ROS) generation, and amyloid metabolism have been implicated in the pathophysiology of sporadic AD. The cellular consequences of mitochondrial dysfunction, however, are not known. To examine these consequences, mitochondrially transformed cells (cybrids) were created from AD patients or disease-free controls. Mitochondria from platelets were fused to 0 cells created by depleting the human neuroblastoma line SH-SY5Y of its mitochondrial DNA (mtDNA). AD cybrids demonstrated a 52% decrease in electron transport chain (ETC) complex IV activity but no difference in complex I activity compared with control cybrids or SH-SY5Y cells. This mitochondrial dysfunction suggests a transferable mtDNA defect associated with AD. ROS generation was elevated in the AD cybrids. AD cybrids also displayed an increased basal cytosolic calcium concentration and enhanced sensitivity to inositol-1,4,5-triphosphate (InsP 3 )-mediated release. Furthermore, they recovered more slowly from an elevation in cytosolic calcium induced by the InsP 3 agonist carbachol. Mitochondrial calcium buffering plays a major role after this type of perturbation. ␤-amyloid (25-35) peptide delayed the initiation of calcium recovery to a carbachol challenge and slowed the recovery rate. Nerve growth factor reduced the carbachol-induced maximum and moderated the recovery kinetics. Succinate increased ETC activity and partially restored the AD cybrid recovery rate. These subtle alterations in calcium homeostasis and ROS generation might lead to increased susceptibility to cell death under circumstances not ordinarily toxic.

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“…From the classical viewpoint, adequate levels of ATP are essential to maintain the neuronal plasma membrane potential via the sodium-potassium ATPase, which consumes about 40% of the energy (1). In addition, mitochondria are an important intracellular Ca 2þ sequestration system (2,3), and especially synaptic mitochondria are indispensible for neurotransmitter reserve pool mobilization in the presynaptic compartment (4). Due to these important features, mitochondria can modulate neuronal excitability and synaptic transmission (5,6).…”

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confidence: 99%

Mitochondrial involvement in neurodegenerative diseases

Kunz

2013

IUBMB Life

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The classical bioenergetical view of the involvement of mitochondria in neurogeneration is based on the fact that mitochondria are the central players of ATP synthesis in neurons and their failure leads to neuronal dysfunction and eventually to cell death. Mutations in at least 39 genes in inherited neurodegenerative disorders seem to alter directly or indirectly mitochondrial function. Most of these mutations do not directly affect oxidative phosphorylation, but act through disturbed mitochondrial dynamics and quality control. This, however, does not invalidate the bioenergetic hypothesis.Neurodegeneration is not necessarily associated with a gross failure of ATP production, but might rather be a consequence of local insufficiencies of ATP supply in critical compartments of neurons, like the presynaptic terminal. We hypothesize that slow disease progression, at least in a subgroup of neurodegenerative diseases, can be explained by the parallel action of subcellular ATP insufficiency and clonal expansion of somatic mitochondrial DNA mutations, and particularly deletions. V C 2013 IUBMB Life, 65(3): [263][264][265][266][267][268][269][270][271][272] 2013

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Regulation of the intracellular free calcium concentration in single rat dorsal root ganglion neurones in vitro.

Abstract: SUMMARY1. Simultaneous whole-cell patch-clamp and Fura-2 microfluorimetric recordings of calcium currents (ICa) and the intracellular free Ca2+ concentration ([Ca2+]i) were made from neurones grown in primary culture from the dorsal root ganglion of the rat. Cells held at -

Cited by 392 publications

References 53 publications

Essential protective role of tumor necrosis factor receptor 2 in neurodegeneration

Essential protective role of tumor necrosis factor receptor 2 in neurodegeneration

Calcium Homeostasis and Reactive Oxygen Species Production in Cells Transformed by Mitochondria from Individuals with Sporadic Alzheimer’s Disease

Mitochondrial involvement in neurodegenerative diseases

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