The Experts below are selected from a list of 46290 Experts worldwide ranked by ideXlab platform
Pak H Chan - One of the best experts on this subject based on the ideXlab platform.
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oxidative damage to the endoplasmic reticulum is implicated in ischemic Neuronal Cell Death
Journal of Cerebral Blood Flow and Metabolism, 2003Co-Authors: Takeshi Hayashi, Atsushi Saito, Shuzo Okuno, Michel Ferranddrake, Robert L Dodd, Tatsuro Nishi, Carolina M Maier, Hiroyuki Kinouchi, Pak H ChanAbstract:The endoplasmic reticulum (ER), which plays important roles in apoptosis, is susceptible to oxidative stress. Because reactive oxygen species (ROS) are robustly produced in the ischemic brain, ER damage by ROS may be implicated in ischemic Neuronal Cell Death. We induced global brain ischemia on wild-type and copper/zinc superoxide dismutase (SOD1) transgenic rats and compared ER stress and Neuronal damage. Phosphorylated forms of eukaryotic initiation factor 2 alpha (eIF2 alpha) and RNA-dependent protein kinase-like ER eIF2 alpha kinase (PERK), both of which play active roles in apoptosis, were increased in hippocampal CA1 neurons after ischemia but to a lesser degree in the transgenic animals. This finding, together with the finding that the transgenic animals showed decreased Neuronal degeneration, indicates that oxidative ER damage is involved in ischemic Neuronal Cell Death. To elucidate the mechanisms of ER damage by ROS, we analyzed glucose-regulated protein 78 (GRP78) binding with PERK and oxidative ER protein modification. The proteins were oxidatively modified and stagnated in the ER lumen, and GRP78 was detached from PERK by ischemia, all of which were attenuated by SOD1 overexpression. We propose that ROS attack and modify ER proteins and elicit ER stress response, which results in Neuronal Cell Death.
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induction of grp78 by ischemic preconditioning reduces endoplasmic reticulum stress and prevents delayed Neuronal Cell Death
Journal of Cerebral Blood Flow and Metabolism, 2003Co-Authors: Takeshi Hayashi, Atsushi Saito, Shuzo Okuno, Michel Ferranddrake, Pak H ChanAbstract:Although the endoplasmic reticulum (ER) is implicated in Neuronal degeneration in some situations, its role in delayed Neuronal Cell Death (DND) after ischemia remains uncertain. The authors speculated that ER stress is involved in DND, that it is reduced by ischemic preconditioning, and that ER stress reduction by preconditioning is due to ER molecular chaperone induction. The phosphorylation status of eukaryotic initiation factor 2α (eIF2α) and RNA-dependent protein kinase–like ER eIF2α kinase (PERK) was investigated in the rat hippocampus after ischemia with and without preconditioning. PERK is phosphorylated by ER stress, which phosphorylates eIF2α. To investigate the role of ER molecular chaperones in preconditioning, the authors examined GRP78 and GRP94 expression, both of which are ER chaperones that inhibit PERK phosphorylation, and compared their induction and ischemic tolerance time windows. Phosphorylation of eIF2α and PERK was confirmed after severe ischemia but was inhibited by preconditionin...
Hisae Kadowaki - One of the best experts on this subject based on the ideXlab platform.
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amyloid beta induces Neuronal Cell Death through ros mediated ask1 activation
Cell Death & Differentiation, 2005Co-Authors: Chiharu Sadamitsu, Atsushi Matsuzawa, Kohsuke Takeda, Hideki Nishitoh, Hisae Kadowaki, Fumihiko Urano, Hiroshi Masutani, Junji YodoiAbstract:Amyloid β (Aβ) is a main component of senile plaques in Alzheimer's disease and induces Neuronal Cell Death. Reactive oxygen species (ROS), nitric oxide and endoplasmic reticulum (ER) stress have been implicated in Aβ-induced neurotoxicity. We have reported that apoptosis signal-regulating kinase 1 (ASK1) is required for ROS- and ER stress-induced JNK activation and apoptosis. Here we show the involvement of ASK1 in Aβ-induced Neuronal Cell Death. Aβ activated ASK1 mainly through production of ROS but not through ER stress in cultured Neuronal Cells. Importantly, ASK1−/− neurons were defective in Aβ-induced JNK activation and Cell Death. These results indicate that ROS-mediated ASK1 activation is a key mechanism for Aβ-induced neurotoxicity, which plays a central role in Alzheimer's disease.
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Amyloid β induces Neuronal Cell Death through ROS-mediated ASK1 activation
Cell Death & Differentiation, 2005Co-Authors: Hisae Kadowaki, Chiharu Sadamitsu, Atsushi Matsuzawa, Kohsuke Takeda, Hideki Nishitoh, Fumihiko Urano, Hiroshi Masutani, Junji Yodoi, Y Urano, T NaganoAbstract:Amyloid β (A β ) is a main component of senile plaques in Alzheimer's disease and induces Neuronal Cell Death. Reactive oxygen species (ROS), nitric oxide and endoplasmic reticulum (ER) stress have been implicated in A β -induced neurotoxicity. We have reported that apoptosis signal-regulating kinase 1 (ASK1) is required for ROS- and ER stress-induced JNK activation and apoptosis. Here we show the involvement of ASK1 in A β -induced Neuronal Cell Death. A β activated ASK1 mainly through production of ROS but not through ER stress in cultured Neuronal Cells. Importantly, ASK1 ^−/− neurons were defective in A β -induced JNK activation and Cell Death. These results indicate that ROS-mediated ASK1 activation is a key mechanism for A β -induced neurotoxicity, which plays a central role in Alzheimer's disease.
Pierre J Talbot - One of the best experts on this subject based on the ideXlab platform.
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pivotal role of receptor interacting protein kinase 1 and mixed lineage kinase domain like in Neuronal Cell Death induced by the human neuroinvasive coronavirus oc43
Journal of Virology, 2017Co-Authors: Mathieu Meessenpinard, Alain Le Coupanec, Marc Desforges, Pierre J TalbotAbstract:Human coronaviruses (HCoV) are respiratory pathogens with neuroinvasive, neurotropic, and neurovirulent properties, highlighting the importance of studying the potential implication of these viruses in neurological diseases. The OC43 strain (HCoV-OC43) was reported to induce Neuronal Cell Death, which may participate in neuropathogenesis. Here, we show that HCoV-OC43 harboring two point mutations in the spike glycoprotein (rOC/Us183-241) was more neurovirulent than the wild-type HCoV-OC43 (rOC/ATCC) in mice and induced more Cell Death in murine and human Neuronal Cells. To evaluate the role of regulated Cell Death (RCD) in HCoV-OC43-mediated neural pathogenesis, we determined if knockdown of Bax, a key regulator of apoptosis, or RIP1, a key regulator of necroptosis, altered the percentage of Neuronal Cell Death following HCoV-OC43 infection. We found that Bax-dependent apoptosis did not play a significant role in RCD following infection, as inhibition of Bax expression mediated by RNA interference did not confer Cellular protection against the Cell Death process. On the other hand, we demonstrated that RIP1 and MLKL were involved in Neuronal Cell Death, as RIP1 knockdown and chemical inhibition of MLKL significantly increased Cell survival after infection. Taken together, these results indicate that RIP1 and MLKL contribute to necroptotic Cell Death after HCoV-OC43 infection to limit viral replication. However, this RCD could lead to Neuronal loss in the mouse CNS and accentuate the neuroinflammation process, reflecting the severity of neuropathogenesis. Importance Because they are naturally neuroinvasive and neurotropic, human coronaviruses are suspected to participate in the development of neurological diseases. Given that the strain OC43 is neurovirulent in mice and induces Neuronal Cell Death, we explored the Neuronal response to infection by characterizing the activation of RCD. Our results revealed that classical apoptosis associated with the Bax protein does not play a significant role in HCoV-OC43-induced Neuronal Cell Death and that RIP1 and MLKL, two Cellular proteins usually associated with necroptosis (an RCD back-up system when apoptosis is not adequately induced), both play a pivotal role in the process. As necroptosis disrupts Cellular membranes and allows the release of damage-associated molecular patterns (DAMP) and possibly induces the production of proinflammatory cytokines, it may represent a proinflammatory Cell Death mechanism that contributes to excessive neuroinflammation and neurodegeneration and eventually to neurological disorders after a coronavirus infection.
Raz Jelinek - One of the best experts on this subject based on the ideXlab platform.
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interactions between bim protein and beta amyloid may reveal a crucial missing link between alzheimer s disease and Neuronal Cell Death
ACS Chemical Neuroscience, 2019Co-Authors: Ravit Malishev, Sukhendu Nandi, Shamchal Bakavayev, Stanislav Engel, Nir Bujanover, Roi Gazit, Dariusz śmilowicz, Nils Metzlernolte, Raz JelinekAbstract:Extensive Neuronal Cell Death is among the pathological hallmarks of Alzheimer’s disease. While neuron Death is coincident with formation of plaques comprising the beta-amyloid (Aβ) peptide, a direct causative link between Aβ (or other Alzheimer’s-associated proteins) and Cell toxicity is yet to be found. Here we show that BIM-BH3, the primary proapoptotic domain of BIM, a key protein in varied apoptotic cascades of which elevated levels have been found in brain Cells of patients afflicted with Alzheimer’s disease, interacts with the 42-residue amyloid isoform Aβ42. Remarkably, BIM-BH3 modulated the structure, fibrillation pathway, aggregate morphology, and membrane interactions of Aβ42. In particular, BIM-BH3 inhibited Aβ42 fibril-formation, while it simultaneously enhanced protofibril assembly. Furthermore, we discovered that BIM-BH3/Aβ42 interactions induced Cell Death in a human neuroblastoma Cell model. Overall, our data provide a crucial mechanistic link accounting for Neuronal Cell Death in Alzheim...
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interactions between bim protein and beta amyloid may reveal a crucial missing link between alzheimer s disease and Neuronal Cell Death
ACS Chemical Neuroscience, 2019Co-Authors: Ravit Malishev, Sukhendu Nandi, Shamchal Bakavayev, Stanislav Engel, Nir Bujanover, Roi Gazit, Dariusz śmilowicz, Nils Metzlernolte, Raz JelinekAbstract:Extensive Neuronal Cell Death is among the pathological hallmarks of Alzheimer’s disease. While neuron Death is coincident with formation of plaques comprising the beta-amyloid (Aβ) peptide, a dire...
Hideki Nishitoh - One of the best experts on this subject based on the ideXlab platform.
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amyloid beta induces Neuronal Cell Death through ros mediated ask1 activation
Cell Death & Differentiation, 2005Co-Authors: Chiharu Sadamitsu, Atsushi Matsuzawa, Kohsuke Takeda, Hideki Nishitoh, Hisae Kadowaki, Fumihiko Urano, Hiroshi Masutani, Junji YodoiAbstract:Amyloid β (Aβ) is a main component of senile plaques in Alzheimer's disease and induces Neuronal Cell Death. Reactive oxygen species (ROS), nitric oxide and endoplasmic reticulum (ER) stress have been implicated in Aβ-induced neurotoxicity. We have reported that apoptosis signal-regulating kinase 1 (ASK1) is required for ROS- and ER stress-induced JNK activation and apoptosis. Here we show the involvement of ASK1 in Aβ-induced Neuronal Cell Death. Aβ activated ASK1 mainly through production of ROS but not through ER stress in cultured Neuronal Cells. Importantly, ASK1−/− neurons were defective in Aβ-induced JNK activation and Cell Death. These results indicate that ROS-mediated ASK1 activation is a key mechanism for Aβ-induced neurotoxicity, which plays a central role in Alzheimer's disease.
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Amyloid β induces Neuronal Cell Death through ROS-mediated ASK1 activation
Cell Death & Differentiation, 2005Co-Authors: Hisae Kadowaki, Chiharu Sadamitsu, Atsushi Matsuzawa, Kohsuke Takeda, Hideki Nishitoh, Fumihiko Urano, Hiroshi Masutani, Junji Yodoi, Y Urano, T NaganoAbstract:Amyloid β (A β ) is a main component of senile plaques in Alzheimer's disease and induces Neuronal Cell Death. Reactive oxygen species (ROS), nitric oxide and endoplasmic reticulum (ER) stress have been implicated in A β -induced neurotoxicity. We have reported that apoptosis signal-regulating kinase 1 (ASK1) is required for ROS- and ER stress-induced JNK activation and apoptosis. Here we show the involvement of ASK1 in A β -induced Neuronal Cell Death. A β activated ASK1 mainly through production of ROS but not through ER stress in cultured Neuronal Cells. Importantly, ASK1 ^−/− neurons were defective in A β -induced JNK activation and Cell Death. These results indicate that ROS-mediated ASK1 activation is a key mechanism for A β -induced neurotoxicity, which plays a central role in Alzheimer's disease.
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ask1 is essential for endoplasmic reticulum stress induced Neuronal Cell Death triggered by expanded polyglutamine repeats
Genes & Development, 2002Co-Authors: Hideki Nishitoh, Atsushi Matsuzawa, Kohsuke Takeda, Kei Tobiume, Kaoru Saegusa, Kiyoshi Inoue, Seiji Hori, Akira KakizukaAbstract:Expansion of CAG trinucleotide repeats that encode polyglutamine is the underlying cause of at least nine inherited human neurodegenerative disorders, including Huntington's disease and spinocerebellar ataxias. PolyQ fragments accumulate as aggregates in the cytoplasm and/or in the nucleus, and induce Neuronal Cell Death. However, the molecular mechanism of polyQ-induced Cell Death is controversial. Here, we show the following: (1) polyQ with pathogenic repeat length triggers ER stress through proteasomal dysfunction; (2) ER stress activates ASK 1 through formation of an IRE1-TRAF2-ASK1 complex; and (3) ASK1(-/-) primary neurons are defective in polyQ-, proteasome inhibitor-, and ER stress-induced JNK activation and Cell Death. These findings suggest that ASK1 is a key element in ER stress-induced Cell Death that plays an important role in the neuropathological alterations in polyQ diseases.