ATP-γ-S-(α,β-CH2) protects against oxidative stress and amyloid beta toxicity in neuronal culture

Danino, Ortal; Grossman, Shlomo; Fischer, Bilha

doi:10.1016/j.bbrc.2015.03.053

Cited by 8 publications

(4 citation statements)

References 33 publications

(46 reference statements)

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“…ATP-γ-S, the non-hydrolysable ATP analog, is a recognized P2 receptor agonist but is also an antioxidant with neuroprotective properties. The chemical modification of this molecule has further increased its antioxidant capacity and stability, making it very interesting to try to reduce neuronal mortality [188][189][190][191]. Hence, both adenosine-and ATP-mediated purinergic signaling seem to be promising ways to treat AD.…”

Section: Discussionmentioning

confidence: 99%

Alzheimer and Purinergic Signaling: Just a Matter of Inflammation?

Merighi

Poloni

Terrazzan

et al. 2021

Cells

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Alzheimer’s disease (AD) is a widespread neurodegenerative pathology responsible for about 70% of all cases of dementia. Adenosine is an endogenous nucleoside that affects neurodegeneration by activating four membrane G protein-coupled receptor subtypes, namely P1 receptors. One of them, the A2A subtype, is particularly expressed in the brain at the striatal and hippocampal levels and appears as the most promising target to counteract neurological damage and adenosine-dependent neuroinflammation. Extracellular nucleotides (ATP, ADP, UTP, UDP, etc.) are also released from the cell or are synthesized extracellularly. They activate P2X and P2Y membrane receptors, eliciting a variety of physiological but also pathological responses. Among the latter, the chronic inflammation underlying AD is mainly caused by the P2X7 receptor subtype. In this review we offer an overview of the scientific evidence linking P1 and P2 mediated purinergic signaling to AD development. We will also discuss potential strategies to exploit this knowledge for drug development.

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Section: Discussionmentioning

confidence: 99%

Alzheimer and Purinergic Signaling: Just a Matter of Inflammation?

Merighi

Poloni

Terrazzan

et al. 2021

Cells

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“…However, despite these encouraging results using antioxidants as neuroprotectants in cell systems [174], beneficial outcomes at the organism level are inconsistent and, in large part, disappointing [175][176][177]. The reasons for those failures are not immediately clear and may have to do with their effective bioavailability and/or antioxidants' effects on physiological roles of ROS in cell signalling, (H 2 O 2 , in particular [178,179]).…”

Section: Ros/h 2 O 2 and Neurodegenerationmentioning

confidence: 99%

Intracellular Sources of ROS/H2O2 in Health and Neurodegeneration: Spotlight on Endoplasmic Reticulum

Konno

Melo

Chambers

et al. 2021

Cells

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Reactive oxygen species (ROS) are produced continuously throughout the cell as products of various redox reactions. Yet these products function as important signal messengers, acting through oxidation of specific target factors. Whilst excess ROS production has the potential to induce oxidative stress, physiological roles of ROS are supported by a spatiotemporal equilibrium between ROS producers and scavengers such as antioxidative enzymes. In the endoplasmic reticulum (ER), hydrogen peroxide (H2O2), a non-radical ROS, is produced through the process of oxidative folding. Utilisation and dysregulation of H2O2, in particular that generated in the ER, affects not only cellular homeostasis but also the longevity of organisms. ROS dysregulation has been implicated in various pathologies including dementia and other neurodegenerative diseases, sanctioning a field of research that strives to better understand cell-intrinsic ROS production. Here we review the organelle-specific ROS-generating and consuming pathways, providing evidence that the ER is a major contributing source of potentially pathologic ROS.

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“…However, increasing evidence has showed that extracellular ATP could be neuroprotective. An analogue of ATP, ATP-γ-S-(α, β-CH2), rescued PC12 cells from oxidative stress injury and amyloid beta-induced toxicity [11]. Besides, extracellular ATP administration protected astrocytes against H 2 O 2 -induced oxidative injury [12], or activated glutamate receptor to modulate synaptic plasticity in the hippocampus [13].…”

Section: Introductionmentioning

confidence: 99%

Extracellular ATP Binding to P2Y1 Receptors Prevents Glutamate-Induced Excitotoxicity: Involvement of Erk1/2 Signaling Pathway to Suppress Autophagy

Xiong

Zhou

Zheng

et al. 2022

Preprint

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Glutamate-induced neuroexcitotoxicity causes neuronal death in neurodegenerative diseases including Alzheimer’s disease and Parkinson’s disease. Extracellular ATP exerts a wide variety of functions, such as attenuating Aβ-mediated toxicity, inhibiting NMDA receptor subunit combinations, and aggravating ischemic brain injury. However, the effect of extracellular ATP on glutamate-induced neuroexcitotoxicity remains largely unknown. Herein, we showed that extracellular ATP prevented the glutamate-induced excitotoxicity via binding to its P2Y1 receptors. We found that excessive glutamate triggered cellular ROS overproduction and mitochondrial membrane potential damage, which were significantly attenuated by extracellular ATP. Besides, glutamate activated autophagy, as illustrated by the increased protein level of autophagic marker LC3II and decreased level of p62, and glutamate-induced neuroexcitotoxicity could be completely abolished by autophagy inhibitor chloroquine. In addition, we revealed that extracellular ATP activated Erk1/2 signaling to suppress autophagy and to exert its neuroprotective effects, which was further reduced by autophagy agonist rapamycin and the selective Erk1/2 inhibitor PD0325901. Taken together, our findings suggest that extracellular ATP binding to P2Y1 receptors protected against glutamate-induced excitotoxicity via Erk1/2-mediated autophagy inhibition, implying the promising potential of ATP for the treatment of neurodegenerative disorders.

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ATP-γ-S-(α,β-CH2) protects against oxidative stress and amyloid beta toxicity in neuronal culture

Cited by 8 publications

References 33 publications

Alzheimer and Purinergic Signaling: Just a Matter of Inflammation?

Alzheimer and Purinergic Signaling: Just a Matter of Inflammation?

Intracellular Sources of ROS/H2O2 in Health and Neurodegeneration: Spotlight on Endoplasmic Reticulum

Extracellular ATP Binding to P2Y1 Receptors Prevents Glutamate-Induced Excitotoxicity: Involvement of Erk1/2 Signaling Pathway to Suppress Autophagy

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