scholarly journals Rola makrofagów i monocytów w infekcji SARS-CoV-2 i w ciężkim przebiegu COVID-19

Kosmos ◽  
2021 ◽  
Vol 70 (3) ◽  
pp. 437-444
Author(s):  
Jacek Z. Kubiak
Keyword(s):  
Α7 Nachr

W tej pracy przeglądowej opisuję, w jaki sposób makrofagi biorą udział zarówno w obronie organizmu przed zakażeniem SARS-CoV-2 i COVID-19 i jak mogą przyczyniać się do ciężkiego przebiegu tej choroby. Makrofagi stanowią pierwszą linię obrony organizmu przed wniknięciem wirusów, w tym koronawirusa SARS-CoV-2. Wywołują one m.in. stan zapalny pozwalający na konsolidację działania całego układu odpornościowego w COVID-19. Makrofagi są jednak również zakażane koronawirusem, a wówczas wydzielają zbyt dużo cytokin i tracą zdolność do wygaszania stanu zapalnego. Nikotyna, działając na receptory nikotynowe ACh α4/α7 (nAChR) może łagodzić prozapalne działanie zakażonych SARS-CoV-2 makrofagów i zmniejszać wywołaną przez nie burzę cytokinową w płucach. Monocyty, które są komórkami prekursorowymi makrofagów, i makrofagi tkankowe mogą przenosić SARS-CoV-2 u pacjentów do takich narządów jak: jądra, najądrza czy trzustka i wywoływać w nich proces zapalny, który w przypadku trzustki może powodować cukrzycę.

scholarly journals Natural Polyhydroxy Flavonoids, Curcuminoids, and Synthetic Curcumin Analogs as α7 nAChRs Positive Allosteric Modulators

2021 ◽  
Vol 22 (2) ◽  
pp. 973
Author(s):  
Marta Ximenis ◽  
José Mulet ◽  
Salvador Sala ◽  
Francisco Sala ◽  
Manuel Criado ◽  
...  
Keyword(s):  
Biological Evaluation ◽  
Allosteric Modulators ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Curcumin Analogues ◽  
Curcumin Derivatives ◽  
Curcumin Analogs ◽  
Naturally Occurring ◽  
Α7 Nachr ◽  
Positive Allosteric Modulators ◽  
Α7 Nachrs

The α7 nicotinic acetylcholine receptor (α7 nAChR) is a ligand-gated ion channel that is involved in cognition disorders, schizophrenia, pain, and inflammation. Allosteric modulation of this receptor might be advantageous to reduce the toxicity in comparison with full agonists. Our previous results obtained with some hydroxy-chalcones, which were identified as positive allosteric modulators (PAMs) of α7 nAChR, prompted us to evaluate the potential of some structurally related naturally occurring flavonoids and curcuminoids and some synthetic curcumin analogues, with the aim of identifying new allosteric modulators of the α7 nAChR. Biological evaluation showed that phloretin, demethoxycurcumin, and bis-demethoxicurcuming behave as PAMs of α7 nAChR. In addition, some new curcumin derivatives were able to enhance the signal evoked by ACh; the activity values found for the tetrahydrocurcuminoid analog 23 were especially promising.

Activation of α7 nicotinic receptor affects APP processing by regulating secretase activity in SH-EP1-α7 nAChR-hAPP695 cells

2010 ◽  
Vol 1356 ◽  
pp. 112-120 ◽  
Author(s):  
Hui Zhen Nie ◽  
Sha Shi ◽  
Ronald J. Lukas ◽  
Wen Juan Zhao ◽  
Yong Ning Sun ◽  
...  
Keyword(s):  
Nicotinic Receptor ◽  
App Processing ◽  
Α7 Nachr ◽  
Secretase Activity

scholarly journals The neuroprotective effects of activated α7 nicotinic acetylcholine receptor against mutant copper–zinc superoxide dismutase 1-mediated toxicity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Taisei Ito ◽  
Masatoshi Inden ◽  
Tomoyuki Ueda ◽  
Yuta Asaka ◽  
Hisaka Kurita ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Motor Neurons ◽  
Superoxide Dismutase 1 ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Neuroprotective Effects ◽  
Nicotinic Acetylcholine ◽  
Copper Zinc Superoxide Dismutase ◽  
Zinc Superoxide Dismutase ◽  
Α7 Nachr ◽  
Copper Zinc

AbstractAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective and progressive loss of motor neurons. Although many drugs have entered clinical trials, few have shown effectiveness in the treatment of ALS. Other studies have shown that the stimulation of α7 nicotinic acetylcholine receptor (nAChR) can have neuroprotective effects in some models of neurodegenerative disease, as well as prevent glutamate-induced motor neuronal death. However, the effect of α7 nAChR agonists on ALS-associated mutant copper–zinc superoxide dismutase 1 (SOD1) aggregates in motor neurons remains unclear. In the present study, we examined whether α7 nAChR activation had a neuroprotective effect against SOD1G85R-induced toxicity in a cellular model for ALS. We found that α7 nAChR activation by PNU282987, a selective agonist of α7 nAChR, exhibited significant neuroprotective effects against SOD1G85R-induced toxicity via the reduction of intracellular protein aggregates. This reduction also correlated with the activation of autophagy through the AMP-activated protein kinase (AMPK)–mammalian target of rapamycin (mTOR) signaling pathway. Furthermore, the activation of α7 nAChRs was found to increase the biogenesis of lysosomes by inducing translocation of the transcription factor EB (TFEB) into the nucleus. These results support the therapeutic potential of α7 nAChR activation in diseases that are characterized by SOD1G85R aggregates, such as ALS.

Potent Antiglioblastoma Agents by Hybridizing the Onium-Alkyloxy-Stilbene Based Structures of an α7-nAChR, α9-nAChR Antagonist and of a Pro-Oxidant Mitocan

2018 ◽  
Vol 61 (23) ◽  
pp. 10531-10544 ◽  
Author(s):  
Francesco Bavo ◽  
Susanna Pucci ◽  
Francesca Fasoli ◽  
Carmen Lammi ◽  
Milena Moretti ◽  
...  
Keyword(s):  
Α7 Nachr

In vitro and in vivo characterization of PheTQS, a novel α7 nAChR positive allosteric modulator

2009 ◽  
Vol 78 (7) ◽  
pp. 913 ◽  
Author(s):  
James N.C. Kew ◽  
Selina Mok ◽  
Annette Weil ◽  
Caterina Virginio ◽  
Laura Castelletti ◽  
...  
Keyword(s):  
Allosteric Modulator ◽  
Positive Allosteric Modulator ◽  
Α7 Nachr ◽  
In Vivo Characterization

scholarly journals B-973, a Novel α7 nAChR Ago-PAM: Racemic and Asymmetric Synthesis, Electrophysiological Studies, and in Vivo Evaluation

2018 ◽  
Vol 9 (11) ◽  
pp. 1144-1148 ◽  
Author(s):  
Sumanta Garai ◽  
Krishnamohan S. Raja ◽  
Roger L. Papke ◽  
Jeffrey R. Deschamps ◽  
M. Imad Damaj ◽  
...  
Keyword(s):  
Asymmetric Synthesis ◽  
In Vivo Evaluation ◽  
Α7 Nachr ◽  
Electrophysiological Studies

scholarly journals Tonic engagement of nicotinic receptors bidirectionally controls striatal spiny projection neuron spike timing

2021 ◽  
Author(s):  
Lior Matityahu ◽  
Jeffrey Malgady ◽  
Meital Schirelman ◽  
Yvonne Johansson ◽  
Jennifer Wilking ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Gaba Release ◽  
Projection Neuron ◽  
Spike Timing ◽  
Projection Neurons ◽  
Striatal Slices ◽  
Cholinergic Interneurons ◽  
Α7 Nachr ◽  
Α7 Nachrs

Striatal spiny projection neurons (SPNs) transform convergent excitatory corticostriatal inputs into an inhibitory signal that shapes basal ganglia output. This process is fine-tuned by striatal GABAergic interneurons (GINs), which receive overlapping cortical inputs and mediate rapid corticostriatal feedforward inhibition of SPNs. Adding another level of control, cholinergic interneurons (CINs), which are also vigorously activated by corticostriatal excitation, can 1) disynaptically inhibit SPNs by activating α4β2 nicotinic acetylcholine receptors (nAChRs) on various GINs and 2) directly modulate corticostriatal synaptic strength via pre-synaptic α7 nAChR receptors. Measurements of the disynaptic inhibitory pathway, however, indicate that it is too slow to compete with direct GIN-mediated feed-forward inhibition. Moreover, functional nAChRs are also present on populations of GINs that do not respond to phasic activation of CINs, such as parvalbumin-positive fast-spiking interneurons (PV-FSIs), making the overall role of nAChRs in shaping striatal synaptic integration unclear. Using acute striatal slices we show that upon synchronous optogenetic activation of corticostriatal projections, blockade of α7 nAChRs delayed SPN spikes, whereas blockade of α4β2 nAChRs advanced SPN spikes and increased postsynaptic depolarizations. The nAChR-dependent inhibition was mediated by downstream GABA release, and data suggest that the GABA source was not limited to GINs that respond to phasic CIN activation. In particular, the observed spike-advancement caused by nAChR blockade was associated with a diminished frequency of spontaneous inhibitory postsynaptic currents in SPNs, and a parallel hyperpolarization of PV-FSIs. Taken together, we describe opposing roles for tonic (as opposed to phasic) engagement of nAChRs in striatal function. We conclude that tonic activation of nAChRs by CINs both sharpens the temporal fidelity of corticostriatal signaling via pre-synaptic α7 nAChRs and maintains a GABAergic brake on cortically-driven striatal output, processes that may shape SPN spike timing, striatal processing and synaptic plasticity.

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