Alzheimer’s amyloid-β peptide disturbs P2X7 receptor-mediated circadian oscillations of intracellular calcium

Wilkaniec, Anna; Schmitt, Karen; Grimm, Amandine; Strosznajder, Joanna B.

doi:10.5114/fn.2016.64813

Cited by 12 publications

(6 citation statements)

References 68 publications

(88 reference statements)

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“…Its acetoxymethyl ester derivative, Fluo-4 AM, easily penetrates plasma membranes, and inside the cells, it is cleaved by esterases to Fluo-4, which becomes highly fluorescent after binding with Ca 2+ . The procedure is essential, as has been described previously by Wilkaniec et al [ 36 ]. SH-SY5Y cells were seeded onto collagen-coated 96-well dark plates at the density of 1.4 × 10 5 cells/ml.…”

Section: Methodsmentioning

confidence: 99%

P2X7 receptor-pannexin 1 interaction mediates extracellular alpha-synuclein-induced ATP release in neuroblastoma SH-SY5Y cells

Wilkaniec

Gąssowska

Czapski

et al. 2017

Purinergic Signalling

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Abnormalities of alpha-synuclein (ASN), the main component of protein deposits (Lewy bodies), were observed in Parkinson’s disease (PD), dementia with Lewy bodies, Alzheimer’s disease, and other neurodegenerative disorders. These alterations include increase in the levels of soluble ASN oligomers in the extracellular space. Numerous works have identified several mechanisms of their toxicity, including stimulation of the microglial P2X7 receptor leading to oxidative stress. While the significant role of purinergic signaling—particularly, P2 family receptors—in neurodegenerative disorders is well known, the interaction of extracellular soluble ASN with neuronal purinergic receptors is yet to be studied. Therefore, in this study, we have investigated the effect of ASN on P2 purinergic receptors and ATP-dependent signaling. We used neuroblastoma SH-SY5Y cell line and rat synaptoneurosomes treated with exogenous soluble ASN. The experiments were performed using spectrofluorometric, radiochemical, and immunochemical methods. We found the following: (i) ASN-induced intracellular free calcium mobilization in neuronal cells and nerve endings depends on the activation of purinergic P2X7 receptors; (ii) activation of P2X7 receptors leads to pannexin 1 recruitment to form an active complex responsible for ATP release; and (iii) ASN greatly decreases the activity of extracellular ecto-ATPase responsible for ATP degradation. Thus, it is concluded that purinergic receptors might be putative pharmacological targets in the molecular mechanism of extracellular ASN toxicity. Interference with P2X7 signaling seems to be a promising strategy for the prevention or therapy of PD and other neurodegenerative disorders.

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Section: Methodsmentioning

confidence: 99%

P2X7 receptor-pannexin 1 interaction mediates extracellular alpha-synuclein-induced ATP release in neuroblastoma SH-SY5Y cells

Wilkaniec

Gąssowska

Czapski

et al. 2017

Purinergic Signalling

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“…P2X7, present on neurons, microglia cells, macrophages, and some lymphocytes, mediates the influx of Ca 2+ and Na + ions into the cell [ 95 , 96 ]. Alzheimer’s Aβ peptide was shown to interfere with the P2X7-mediated circadian rhythms of the intracellular calcium levels [ 97 ]. Furthermore, recent results [ 98 ] show that activation of P2X7 affects alpha-synuclein (ASN)-induced intracellular free calcium mobilization in neuronal cells and leads to the formation of the active complex by pannexin 1, responsible for ATP release.…”

Section: Receptors P2xmentioning

confidence: 99%

Role of purinergic receptors in the Alzheimer’s disease

Cieślak¹,

Wojtczak

2018

Purinergic Signalling

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Etiology of the Alzheimer’s disease (AD) is not fully understood. Different pathological processes are considered, such as amyloid deposition, tau protein phosphorylation, oxidative stress (OS), metal ion disregulation, or chronic neuroinflammation. Purinergic signaling is involved in all these processes, suggesting the importance of nucleotide receptors (P2X and P2Y) and adenosine receptors (A1, A2A, A2B, A3) present on the CNS cells. Ecto-purines, ecto-pyrimidines, and enzymes participating in their metabolism are present in the inter-cellular spaces. Accumulation of amyloid-β (Aβ) in brain induces the ATP release into the extra-cellular space, which in turn stimulates the P2X7 receptors. Activation of P2X7 results in the increased synthesis and release of many pro-inflammatory mediators such as cytokines and chemokines. Furthermore, activation of P2X7 leads to the decreased activity of α-secretase, while activation of P2Y2 receptor has an opposite effect. Simultaneous inhibition of P2X7 and stimulation of P2Y2 would therefore be the efficient way of the α-secretase activation. Activation of P2Y2 receptors present in neurons, glia cells, and endothelial cells may have a positive neuroprotective effect in AD. The OS may also be counteracted via the purinergic signaling. ADP and its non-hydrolysable analogs activate P2Y13 receptors, leading to the increased activity of heme oxygenase, which has a cytoprotective activity. Adenosine, via A1 and A2A receptors, affects the dopaminergic and glutaminergic signaling, the brain-derived neurotrophic factor (BNDF), and also changes the synaptic plasticity (e.g., causing a prolonged excitation or inhibition) in brain regions responsible for learning and memory. Such activity may be advantageous in the Alzheimer’s disease.

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“…The activation of these ionotropic receptors is significant for Ca 2+ -induced intracellular signalling pathways [7,8] involved in physiological processes or pathological conditions [9]. Growing evidence shows that P2X receptors play an important role in neurodegenerative diseases [10]. Particularly, P2X7 receptor (P2X7R)-mediated signalling may exert important roles in PD-related neurodegeneration [3,11].…”

Section: Introductionmentioning

confidence: 99%

P2X7 Receptor is Involved in Mitochondrial Dysfunction Induced by Extracellular Alpha Synuclein in Neuroblastoma SH-SY5Y Cells

Wilkaniec

Cieślik

Murawska

et al. 2020

IJMS

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The purinergic P2X7 receptor (P2X7R) belongs to a family of trimeric ion channels that are gated by extracellular adenosine 5′-triphosphate (ATP). Several studies have pointed to a role of P2X7R-dependent signalling in Parkinson's disease (PD)-related neurodegeneration. The pathology of (PD) is characterized by the formation of insoluble alpha-synuclein (α-Syn) aggregates—Lewy bodies, but the mechanisms underlying α-Syn-induced dopaminergic cell death are still partially unclear. Our previous studies indicate that extracellular α-Syn directly interact with neuronal P2X7R and induces intracellular free calcium mobilization in neuronal cells. The main objective of this study was to examine the involvement of P2X7R receptor in α-Syn-induced mitochondrial dysfunction and cell death. We found that P2X7R stimulation is responsible for α-Syn-induced oxidative stress and activation of the molecular pathways of programmed cell death. Exogenous α-Syn treatment led to P2X7R-dependent decrease in mitochondrial membrane potential as well as elevation of mitochondrial ROS production resulting in breakdown of cellular energy production. Moreover, P2X7R-dependent deregulation of AMP-activated protein kinase as well as decrease in parkin protein level could be responsible for α-Syn-induced mitophagy impairment and accumulation of dysfunctional mitochondria. P2X7R might be putative pharmacological targets in molecular mechanism of extracellular α-Syn toxicity.

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Alzheimer’s amyloid-β peptide disturbs P2X7 receptor-mediated circadian oscillations of intracellular calcium

Abstract: A b s t r a c t Recent data indicate that Alzheimer's disease (AD) is associated with disturbances of the circadian rhythm in patients.We examined the effect of amyloid-β (Aβ)

Cited by 12 publications

References 68 publications

P2X7 receptor-pannexin 1 interaction mediates extracellular alpha-synuclein-induced ATP release in neuroblastoma SH-SY5Y cells

P2X7 receptor-pannexin 1 interaction mediates extracellular alpha-synuclein-induced ATP release in neuroblastoma SH-SY5Y cells

Role of purinergic receptors in the Alzheimer’s disease

P2X7 Receptor is Involved in Mitochondrial Dysfunction Induced by Extracellular Alpha Synuclein in Neuroblastoma SH-SY5Y Cells

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