Anti-inflammatory role of microglial alpha7 nAChRs and its role in neuroprotection

Egea, Javier; Buendía, Izaskun; Parada, Esther; Navarro, Elisa; León, Rafael; López, Manuela G.

doi:10.1016/j.bcp.2015.07.032

Cited by 254 publications

(200 citation statements)

References 149 publications

(179 reference statements)

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“…This finding, together with the usual young disease onset of dyskinetic patients2, might support the notion of a neuroprotective effect of the cholinergic system on nigrostriatal dopamine‐containing neurons 49, 50, 51. In this study, we were not able to properly address a putative neuroprotective effect of the cholinergic system on nigrostriatal dopamine‐containing neurons and disease progression.…”

Section: Discussionmentioning

confidence: 61%

Cholinergic activity and levodopa‐induced dyskinesia: a multitracer molecular imaging study

Brumberg

Küsters

Al‐Momani

et al. 2017

Ann Clin Transl Neurol

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ObjectiveTo investigate the association between levodopa‐induced dyskinesias and striatal cholinergic activity in patients with Parkinson's disease.MethodsThis study included 13 Parkinson's disease patients with peak‐of‐dose levodopa‐induced dyskinesias, 12 nondyskinetic patients, and 12 healthy controls. Participants underwent 5‐[123I]iodo‐3‐[2(S)‐2‐azetidinylmethoxy]pyridine single‐photon emission computed tomography, a marker of nicotinic acetylcholine receptors, [123I]N‐ω‐fluoropropyl‐2β‐carbomethoxy‐3β‐(4‐iodophenyl)nortropane single‐photon emission computed tomography, to measure dopamine reuptake transporter density and 2‐[18F]fluoro‐2‐deoxyglucose positron emission tomography to assess regional cerebral metabolic activity. Striatal binding potentials, uptake values at basal ganglia structures, and correlations with clinical variables were analyzed.ResultsDensity of nicotinic acetylcholine receptors in the caudate nucleus of dyskinetic subjects was similar to that of healthy controls and significantly higher to that of nondyskinetic patients, in particular, contralaterally to the clinically most affected side.InterpretationOur findings support the hypothesis that the expression of dyskinesia may be related to cholinergic neuronal excitability in a dopaminergic‐depleted striatum. Cholinergic signaling would play a role in maintaining striatal dopaminergic responsiveness, possibly defining disease phenotype and progression.

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Section: Discussionmentioning

confidence: 61%

Cholinergic activity and levodopa‐induced dyskinesia: a multitracer molecular imaging study

Brumberg

Küsters

Al‐Momani

et al. 2017

Ann Clin Transl Neurol

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“…In addition, nAChA7Rs have neuroprotective anti-inflammatory role (Egea et al, 2015), and a reduced activation of anti-inflammatory pathway due to their lower expression could result in abnormal brain metabolism and consequently lead to altered functional coupling between the regions.…”

Section: Nacha7r Activation Results In Ca2+ Influx and A Consequent Fmentioning

confidence: 99%

An acetylcholine alpha7 positive allosteric modulator rescues a schizophrenia-associated brain endophenotype in the 15q13.3 microdeletion, encompassing CHRNA7

Gass

Weber‐Fahr

Sartorius

et al. 2016

European Neuropsychopharmacology

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“…The mechanisms that link the early increase in cytosolic Ca 2ϩ with the final anti-inflammatory effects have not yet been completely elucidated (14, 54 -56). ␣7 nAChR has been shown to modulate several signaling pathways, such as JAK2/STAT3/NF-B, PLC/ inositol 1,4,5-trisphosphate, and PI3K/Akt/Nrf-2 pathways, which in immune cells result in potent anti-inflammatory effects through inflammatory cytokine production inhibition and overexpression of hemooxigenase-1 (54,(57)(58)(59). Also, a direct coupling of ␣7 nAChR to G-protein has been recently described (60,61).…”

Section: Discussionmentioning

confidence: 99%

Expression and Functional Role of α7 Nicotinic Receptor in Human Cytokine-stimulated Natural Killer (NK) Cells

Zanetti

Ziblat

Torres

et al. 2016

Journal of Biological Chemistry

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The homomeric ␣7 nicotinic receptor (nAChR) is one of the most abundant nAChRs in the central nervous system where it contributes to cognition, attention, and working memory. ␣7 nAChR is also present in lymphocytes, dendritic cells (DCs), and macrophages and it is emerging as an important drug target for intervention in inflammation and sepsis. Natural killer (NK) cells display cytotoxic activity against susceptible target cells and modulate innate and adaptive immune responses through their interaction with DCs. We here show that human NK cells also express ␣7 nAChR. ␣7 nAChR mRNA is detected by RT-PCR and cell surface expression of ␣7 nAChR is detected by confocal microscopy and flow cytometry using ␣-bungarotoxin, a specific antagonist. Both mRNA and protein levels increase during NK stimulation with cytokines (IL-12, IL-18, and IL-15). Exposure of cytokine-stimulated NK cells to PNU-282987, a specific ␣7 nAChR agonist, increases intracellular calcium concentration ([Ca2؉

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Anti-inflammatory role of microglial alpha7 nAChRs and its role in neuroprotection

Cited by 254 publications

References 149 publications

Cholinergic activity and levodopa‐induced dyskinesia: a multitracer molecular imaging study

Cholinergic activity and levodopa‐induced dyskinesia: a multitracer molecular imaging study

An acetylcholine alpha7 positive allosteric modulator rescues a schizophrenia-associated brain endophenotype in the 15q13.3 microdeletion, encompassing CHRNA7

Expression and Functional Role of α7 Nicotinic Receptor in Human Cytokine-stimulated Natural Killer (NK) Cells

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