bp(GO:"cell death")
Picomolar levels of Abeta can also rescue neuronal cell death induced by inhibition of Abeta generation (by exposure to inhibitors of beta- or gamma-scretases) [160], possibly through regulating the potassium ion channel expression, hence affecting neuronal excitability [161] PubMed:21214928
Many studies have documented that AICD is cytotoxic and that over-expressing different AICDs (C31, C57, C59) in Hela, H4, N2a or PC12 cell lines, as well as neuronal cell lines, induces cell death (Lu et al. 2000) PubMed:22122372
In the brain, however, Cox2 is constitutively expressed by neurons (212, 512), participates in modulating synaptic plasticity (53, 464), and conditionally can either inhibit or promote cell death (74, 85, 237, 322, 451). PubMed:19126755
Nicotine protects SH-SY5Y cells from cell death induced by thapsigargin, an inhibitor of the sarcoplasmic-reticulum calcium pump (Arias et al., 2004). PubMed:19293145
Nicotinic neuroprotection against non-Abeta toxicity is also mediated largely through alpha7 nAChRs. alpha7 nAChRs protect PC12 cells against ethanol toxicity (Li et al., 1999a) and from cell death associated with serum depletion (Ren et al., 2005); they protect cultured neurons against glutamate-induced excitotoxicity (Kaneko et al., 1997) and hippocampal slices against oxygen and glucose deprivation (Egea et al., 2007) through the activation of alpha7 nAChRs (Rosa et al., 2006). PubMed:19293145
Nicotinic neuroprotection against non-Abeta toxicity is also mediated largely through alpha7 nAChRs. alpha7 nAChRs protect PC12 cells against ethanol toxicity (Li et al., 1999a) and from cell death associated with serum depletion (Ren et al., 2005); they protect cultured neurons against glutamate-induced excitotoxicity (Kaneko et al., 1997) and hippocampal slices against oxygen and glucose deprivation (Egea et al., 2007) through the activation of alpha7 nAChRs (Rosa et al., 2006). PubMed:19293145
The popular amyloid cascade hypothesis posits that the gradual build-up of Abeta plaques leads to neuronal inflammation, dysfunction, and, eventually, cell death. The two brain regions most critically affected by this degeneration are the cortex and hippocampus, both of which are involved in cognition, learning, and memory. PubMed:24511233
In the dopamine-producing neuroblastoma cell line SH-SY5Y, Parkin rescued the cells from p38-induced cell death PubMed:14556719
Activation of M1 mAChR also protects against apoptotic factors in human neuroblastoma SH-SY5Y cells, such as DNA damage, oxidative stress, caspase activation, and mitochondrial impairment[83]. In addition, apoptosis induced by serum deprivation is blocked by M1 mAChR activation in a phosphoinositide 3-kinase- and MAPK/ERKindependent manner PubMed:24590577
It has been shown that Abeta can be degraded by the proteasome in cultured neurons and astrocytes, and reatment with the proteasome inhibitor lactacystin decreased viability of cells exposed to Abeta (Lopez Salon et al., 2003). PubMed:14556719
It then aggregates, and the insoluble protein elicits cell death via the Unfolded Protein Response (UPR). PubMed:14556719
In the dopamine-producing neuroblastoma cell line SH-SY5Y, Parkin rescued the cells from p38-induced cell death PubMed:14556719
Administration of cystamine, a transglutaminase inhibitor, can reduce aggregate formation and death in cells expressing atrophin-1 (DRPLA model) (Igarashi et al., 1998) and in cells expressing mutant androgen receptor (SBMA model) (Mandrusiak et al., 2003). PubMed:14556719
Administration of cystamine, a transglutaminase inhibitor, can reduce aggregate formation and death in cells expressing atrophin-1 (DRPLA model) (Igarashi et al., 1998) and in cells expressing mutant androgen receptor (SBMA model) (Mandrusiak et al., 2003). PubMed:14556719
Thus, exposure to lactacystin resulted in increased cell death in human cell lines expressing mutant SOD1 (Aquilano et al., 2003; Hyun et al., 2003). PubMed:14556719
Similarly, overexpression of the putative SOD1 E3 ligase dorfin can inhibit cell death induced by the mutant protein (Niwa et al., 2002), presumably by promoting its removal via the UPS. PubMed:14556719
Overexpression of the chaperone HSP70 has been found to reduce aggregate formation and death in nonneuronal cultured cells expressing mutant SOD1 (Bruening et al.,1999). PubMed:14556719
Tentative support for this idea was obtained in a cell model of HD, where expression of a dominant-negative variant of the E2 Cdc34p decreased the formation of intranuclear inclusions but increased the likelihood of cell death (Saudou et al., 1998). PubMed:14556719
It then aggregates, and the insoluble protein elicits cell death via the Unfolded Protein Response (UPR). PubMed:14556719
Similarly, overexpression of the putative SOD1 E3 ligase dorfin can inhibit cell death induced by the mutant protein (Niwa et al., 2002), presumably by promoting its removal via the UPS. PubMed:14556719
Interestingly, the expression of the inactive E3 increased the number of the dying Purkinje cells PubMed:14556719
Tau-containing neurofibrillary tangle (NFT) accumulation is the closest correlate with cognitive decline and cell loss (Arriagada et al., 1992), yet mechanisms mediating tau toxicity are poorly understood PubMed:30126037
NFT containing neurons upregulated genes involved in cell survival and viability, inflammation, cell cycle progression and molecular transport and downregulated apoptosis, necrosis and cell death pathways (Figure 1a). NFkB, a pro-survival master transcriptional regulator of inflammation, was the highest predicted upstream regulator of the NFT-gene expression profile. In agreement with inflammatory activation, other predicted upstream regulators included IFNG, TNF, TLR4, IL1B and CXCL1 (Figure 1b) PubMed:30126037
While evidence has linked FTD with parkinsonism in patients to tau mutations on chromosome 17 (FTDP-17), implying that tau dysfunction alone can cause neurodegeneration (Reed et al., 2001), studies in animal models have shown that overexpression of tau can lead to cell death (Lee et al., 2001; Tanemura et al., 2001, 2002; Tatebayashi et al., 2002) and exhibit behavioral abnormalities and synaptic dysfunction without the presence of NFTs (Wittmann et al., 2001; Andorfer et al., 2003; Santacruz et al., 2005; Spires et al., 2006; Berger et al., 2007; Yoshiyama et al., 2007; Cowan et al., 2010) PubMed:28420982
There was no difference in cell viability between tau-aggregate positive and negative cells for up to 4 days (Supplementary Fig. 10). PubMed:26458742
In human astrocytes, ATP released from damaged or dying cells after traumatic brain injury activates the NLRP2 inflammasome, leading to the maturation of both IL-1β and IL-18 (Minkiewicz et al., 2013) PubMed:24561250
PP2A plays a critical role in cellular physiology including cell cycle regulation, cell proliferation and death, development, cytoskeleton dynamics, cell mobility, and regulation of multiple signal transduction pathways PubMed:19277525
Misfolded α-synuclein proteins form insoluble oligomers, which in turn lead to the cascade of pathogenic neurotoxicity-induced responses such as neuroinflammation and cell death [55] PubMed:29758300
However, in another study, iPSC-derived tau A152T and MAPT IVS 10+16 (a tau splice mutant) cortical neurons had increased cell death in response to rapamycin treatment, although basal cell death was ∼10 times higher in these tau mutants relative to controls, making interpretation of the work difficult [134]. PubMed:29758300
Additionally, PN regulation is integrated with pathways involved in inflam- mation, response to oxidative stress, caloric restriction/starvation, and longevity. PubMed:23746257
It has been inferred that aggresome formation in vitro is a cytoprotective response in cultured cells since their formation correlates inversely with cell death, whereas interventions that block aggresome formation enhance cytotoxicity and slow the rate of turnover of misfolded proteins [27,64,70–72] PubMed:18930136
Recent advances have demonstrated that autophagy also serves a surprisingly diverse array of additional functions, including organelle clearance, antigen presentation, elimination of microbes, as well as regulation of development and cell death [9]. PubMed:18930136
The three sensors of ER proteotoxic stress facilitate contra- dictory responses since they either promote cell survival by decreasing the misfolded protein and/or oxidative load, or, if UPR fails, they promote the activation of apoptotic pathways that eventually result in cell death [57]. PubMed:24563850
The three sensors of ER proteotoxic stress facilitate contra- dictory responses since they either promote cell survival by decreasing the misfolded protein and/or oxidative load, or, if UPR fails, they promote the activation of apoptotic pathways that eventually result in cell death [57]. PubMed:24563850
In our hands, these aggregated tau species formed in different conditions did not show any significant release of LDH when applied on the differentiated SH-SY5Y cells (Supplementary Fig. 8A), and they did not show a significant reduction in cell viability by the MTTassay (Supplementary Fig. 8B). PubMed:28528849
To address this question, we first applied the oligomers directly after the purification of the protein eluting from the Butyl FF 16/ 10 column (without buffer exchange; 1, 5, and 10 mM) to SHSY5Y cells and observed a variety of toxic effects, including pronounced reduction in the cell viability (by MTT assay, Fig. 3A), increase in apoptotic cells (by Hoechst staining, Supplementary Fig. 4A), loss of mitochondrial membrane potential (by JC1 assay, Supplementary Fig. 4B), caspase 3/7 activation (Supplementary Fig. 4C-D), and cytochrome-c release (Supplementary Fig. 4), within 5 hours of incubation. PubMed:28528849
Consistent with this, NeuN staining of the slices fixed after 48 hours of treatment with TauRDΔK oligomers revealed no reduction in the neuronal number in all regions of the hippocampus (CA1, CA3, and DG) (Fig. 3C and D, Supplementary Fig. 7), confirming that TauRDΔK oligomers do not cause cell death in the OHSC model as well. PubMed:28528849
Toxicity assays revealed that neither CHIP nor any of the tau constructs caused cell death compared to the control GFP vector (Supplementary Fig. 1). PubMed:25374103
Toxicity assays revealed that neither CHIP nor any of the tau constructs caused cell death compared to the control GFP vector (Supplementary Fig. 1). PubMed:25374103
Toxicity assays revealed that neither CHIP nor any of the tau constructs caused cell death compared to the control GFP vector (Supplementary Fig. 1). PubMed:25374103
Toxicity assays revealed that neither CHIP nor any of the tau constructs caused cell death compared to the control GFP vector (Supplementary Fig. 1). PubMed:25374103
Exposure of primary neuronal cells or post-mitotic neurons to Aβ1-42 peptide has been shown to strongly activate the p50:p65 dimers and mediate neuronal cell death (Fig 1) PubMed:25652642
Due to these properties, LPS can easily be incorporated into the membrane of (red blood) cells, alter their membrane properties, and thus promote cell death [123, 124]. PubMed:29956069
Moreover, in the current study, we identified a crucial role of Hri in protecting erythroid precursors during differentiation by promoting terminal maturation including enucleation, preventing cell death, and increasing iron availability for erythropoiesis. PubMed:25411909
It then aggregates, and the insoluble protein elicits cell death via the Unfolded Protein Response (UPR). PubMed:14556719
In human astrocytes, ATP released from damaged or dying cells after traumatic brain injury activates the NLRP2 inflammasome, leading to the maturation of both IL-1β and IL-18 (Minkiewicz et al., 2013) PubMed:24561250
Additionally, PN regulation is integrated with pathways involved in inflam- mation, response to oxidative stress, caloric restriction/starvation, and longevity. PubMed:23746257
It has been inferred that aggresome formation in vitro is a cytoprotective response in cultured cells since their formation correlates inversely with cell death, whereas interventions that block aggresome formation enhance cytotoxicity and slow the rate of turnover of misfolded proteins [27,64,70–72] PubMed:18930136
Moreover, in the current study, we identified a crucial role of Hri in protecting erythroid precursors during differentiation by promoting terminal maturation including enucleation, preventing cell death, and increasing iron availability for erythropoiesis. PubMed:25411909
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.