ライフサイエンスコーパス: alpha7 nAChR

1 alpha7 nAChR is also present in lymphocytes, dendritic c

2 alpha7 nAChR mRNA is detected by RT-PCR and cell surface

3 alpha7 nAChR, CFTR, and adenylyl cyclase-1 are physicall

4 alpha7 nAChRs are expressed widely throughout the brain,

5 alpha7 nAChRs at the TSC may act as a sensor for spillov

6 alpha7 nAChRs have a very low probability of channel act

7 alpha7-nAChRs are downstream of IL-13 but upstream of GA

8 quin oline-8-sulfonamide (4BP-TQS) activate alpha7 nAChRs more slowly and cause only low levels of a

9 hese novel findings indicate that activating alpha7 nAChR is a promising treatment for cognitive impa

10 d function of the nicotinic receptor alpha7 (alpha7-nAChR).

11 a7 nAChRs and is recapitulated by GTS-21, an alpha7 nAChR partial agonist.

12 ne and NS1738 was mimicked by PNU-282987 (an alpha7 nAChR agonist), and was absent in alpha7 nAChR kn

13 However, an alpha7 nAChR antagonist had no effect at any age.

14 that nicotine in combination with NS1738, an alpha7 nAChR-positive allosteric modulator, strongly pot

15 Maximal transient probability of an alpha7 nAChR being open with rapid agonist applications

16 tential of (18)F-ASEM ((18)F-JHU82132) as an alpha7-nAChR radioligand for PET.

17 SSR180711, an alpha7-nAChR-selective partial agonist, blocked (18)F-AS

18 Pharmacological inhibition using an alpha7-nAChR antagonist or genetic deletion of nAChR alp

19 00-fold selectivity over the alpha3beta2 and alpha7 nAChR subtypes.

20 ts mediated by alpha3beta4, alpha3beta2, and alpha7 nAChR subtypes.

21 he other major subtypes, the alpha4beta2 and alpha7 nAChR.

22 ditory gating deficits in schizophrenia, and alpha7 nAChR agonists can potentially reverse these defi

23 d both beta2 subunit-containing (beta2*) and alpha7 nAChRs in the effects of nicotine in models of an

24 >1 microM, also inhibits these receptors and alpha7 nAChRs.

25 -component combination of PMCA2, PSD-95, and alpha7-nAChR offers a novel mechanism for tight control

26 In vivo cerebral binding of (18)F-ASEM and alpha7-nAChR expression in mutant DISC1 mice, a rodent m

27 ncreased the levels of alpha7-nAChR mRNA and alpha7-nAChR transcription in human SCC-L cell lines and

28 l prefrontal cortex and substantia nigra and alpha7-nAChR binding in the lateral and ventromedial hyp

29 pha7 subunit protein on the cell surface and alpha7-nAChR function, but not alpha7 subunit mRNA, sugg

30 mucus formation is independent of IL-13, and alpha7-nAChRs are critical in airway mucous cell metapla

31 Acetylcholine and alpha7-nAChRs might serve as therapeutic targets to cont

32 beta2-nAChR relative to the alpha3beta4- and alpha7-nAChRs than 5a and 5g.

33 for alpha4beta2-nAChR over alpha3beta4- and alpha7-nAChRs.

34 tagonists at alpha4beta2-, alpha3beta4-, and alpha7-nAChRs.

35 ere evident, with most compounds emerging as alpha7 nAChR agonists and alpha4beta2 nAChR antagonists.

36 trafficking of alpha7 subunits and assembled alpha7-nAChRs to the cell surface.

37 ine receptors (nAChRs) and a full agonist at alpha7 nAChRs.

38 Because alpha7-nAChRs have a high permeability to Ca(2+), we per

39 to examine further the relationship between alpha7-nAChR availability and MCI.

40 r intracellular calcium signaling but not by alpha7 nAChR antagonists.

41 Hence, LTP was prevented by alpha7 nAChR antagonists dihydro-beta-erythroidine and m

42 TFTs, is essential for their recognition by alpha7 nAChR, although it is less important for interact

43 c neurotransmission in the brain mediated by alpha7 nAChRs and that this has a profound effect on reg

44 2* nAChRs, whereas ACh responses mediated by alpha7 nAChRs were not hampered.

45 fibers elicits synaptic currents mediated by alpha7 nAChRs.

46 egulation of signal transduction pathways by alpha7 nAChRs in cells such as those that regulate infla

47 -surface expression and calcium signaling by alpha7 nAChRs.

48 f endogenous PPARalpha ligands, triggered by alpha7-nAChR activation, blocks in rats nicotine-induced

49 at the binding of (18)F-ASEM was mediated by alpha7-nAChRs and the radioligand was suitable for drug

50 In contrast, STN neurons containing alpha7 nAChRs (alpha7 neurons) received more GABAergic i

51 need for the technical capability to control alpha7 nAChR gene expression.

52 deletions and duplications lead to decreased alpha7 nAChR-associated calcium flux.

53 excision is an effective approach to delete alpha7 nAChR expression in a cell-specific manner.

54 nd orthosteric agonists results in different alpha7 nAChRs open-channel conformations.

55 tive recruiters and activators of endogenous alpha7 nAChR-dependent cholinergic pathways to reduce br

56 ns enhanced surface expression of endogenous alpha7 nAChRs, while a combination of chemotherapeutic B

57 rove cognition in schizophrenia by enhancing alpha7 nAChR function may require consideration of these

58 Here we explore alpha7-nAChR localization and actions in primate dlPFC a

59 e here show that human NK cells also express alpha7 nAChR.

60 nsitization kinetics of native and expressed alpha7 nAChRs.

61 ponse to acetylcholine in oocytes expressing alpha7 nAChRs with an IC50 of 3.24 +/- 0.7 muM.

62 d neuroadaptations; conversely, facilitating alpha7 nAChRs activation specifically in the VTA promote

63 EPSC decay time and prolonged both the fast (alpha7-nAChR-mediated) and slow (alpha3*-nAChR-mediated)

64 Finally, alpha7-nAChR was expressed at significantly higher level

65 7(LBDEx4007Ehs)) which we refer to as floxed alpha7 nAChR conditional knockout or alpha7nAChR(flox).

66 vity, the highest-potency building block for alpha7 nAChRs, i.e., 3alpha-azido-N-methylammonium tropa

67 entified NACHO as an essential chaperone for alpha7 nAChRs.

68 -beta-erythroidine that was not observed for alpha7 nAChRs at comparable concentrations.

69 nes and aromatic groups were most potent for alpha7 nAChRs.

70 were generally ~2-fold lower than those for alpha7 nAChRs.

71 y for alpha4beta2-nAChR and low affinity for alpha7-nAChR.

72 the currently available PET radioligands for alpha7-nAChR are suitable for quantitative PET imaging,

73 ylcholine might be the biological ligand for alpha7-nAChRs to trigger airway mucus formation.

74 pposed to being incorporated into functional alpha7 nAChRs at the cell membrane.

75 inals, indicating the presence of functional alpha7 nAChRs at presynaptic terminals.

76 ost-translational upregulation of functional alpha7-nAChRs.

77 The effects on release require functional alpha7-nAChRs and may to depend on CAST/ELKS (calpastati

78 drugs demonstrated that [(18)F]7a is highly alpha7-nAChR selective.

79 aggression, and demonstrate that hippocampal alpha7 nAChR signaling is necessary and sufficient to li

80 nt existing receptor subtypes, the homomeric alpha7 nAChR has attracted considerable attention becaus

81 ncatenated (alpha7)5-nAChRs or for homomeric alpha7-nAChRs constituted from unlinked alpha7 subunits.

82 mpared pharmacological profiles of homomeric alpha7-nAChRs and alpha7beta2-nAChRs.

83 g memory; however, little is known about how alpha7-nAChRs influence dlPFC cognitive circuits.

84 ation using Xenopus oocytes expressing human alpha7 nAChR with a two-electrode voltage clamp.

85 g ligand binding to channel opening in human alpha7 nAChR.

86 in AChBP and, by extrapolation, in the human alpha7 nAChR as determined by electrophysiology measurem

87 d substantially reduced potency at the human alpha7 nAChR relative to alpha-GID, a desirable feature

88 electrophysiological recordings on the human alpha7 nAChR we demonstrate that the identified fragment

89 acellular ligand-binding domain of the human alpha7 nAChR, to investigate the structural determinants

90 t unbinding are transmitted within the human alpha7 nAChR.

91 0.03 mum) and with lower efficiency to human alpha7 nAChR (IC(50) 22 +/- 2 mum).

92 sitive allosteric modulators (PAMs) of human alpha7 nAChRs expressed in Xenopus ooctyes.

93 tress bidirectional interplay and identifies alpha7 nAChRs as a promising therapeutic target for stre

94 Here we identify alpha7 nAChR as a key regulator of CFTR in the airways.

95 These data further implicate alpha7 nAChRs in regulation of aggression, and demonstra

96 (an alpha7 nAChR agonist), and was absent in alpha7 nAChR knock-out mice.

97 nd NIC intake, suggesting that a decrease in alpha7 nAChR function increases motivation to work for N

98 For deletions, this decrease in alpha7 nAChR-dependent calcium flux is expected due to h

99 dy was aimed at addressing which residues in alpha7-nAChRs potentially interact with Abeta to regulat

100 in the plasma of average smokers) increased alpha7-nAChR levels in human SCC-L cell lines.

101 tanus toxin to individual synapses increases alpha7-nAChR dwell time at presynaptic sites.

102 nAChRs by demonstrating that choline-induced alpha7 nAChR currents were present in Cre-negative, but

103 Abeta exposure-induced alpha7-nAChR functional upregulation occurs before there

104 oreover, expression of the anti-inflammatory alpha7-nAChR (alpha7-nicotinic acetylcholine receptor) w

105 imits for intoxication in humans can inhibit alpha7 nAChRs in LDTg neurons from rats.

106 a well characterized conotoxin that inhibits alpha7 nAChRs, on differentiated THP-1 pre-monocyte macr

107 This novel mechanism involving alpha7-nAChRs in mediation of Abeta effects provides pot

108 ed decay times of pharmacologically isolated alpha7-nAChR- and alpha3*-nAChR-EPSCs.

109 ed the baboon brain and specifically labeled alpha7-nAChR.

110 red the mouse brain and specifically labeled alpha7-nAChRs.

111 As a result, mice lacking alpha7-nAChRs have an altered balance in the excitatory/

112 results demonstrate that Bcl-2 proteins link alpha7 nAChR assembly to cell survival pathways.

113 ing nAChRs, but through distinct mechanisms: alpha7-nAChRs affect only the termination of spontaneous

114 Agonist-induced responses of Tyr-93 mutant alpha7-nAChRs indicated possible interactions of nicotin

115 onger peptides inhibited muscle-type nAChRs, alpha7 nAChRs, and alpha3beta2 nAChRs in the micromolar

116 fects of 2'- and 4'-methylations on nicotine alpha7 nAChR interaction might be exploited for the desi

117 The mouse blocking studies with non-alpha7-nAChR central nervous system drugs demonstrated t

118 ctivation of presynaptic alpha4beta2 but not alpha7 nAChRs in the DRN.

119 al processing involves alpha4beta2*, but not alpha7, nAChRs, whereas both receptor subtypes regulate

120 ow that the effects of beta2-nAChRs, but not alpha7-nAChRs, are mediated through the activation of GA

121 We also observed alpha7 nAChR-mediated calcium rises at mossy fiber giant

122 nged nicotine exposure mimics the absence of alpha7 nAChR in mice or its inactivation in vitro in hum

123 oth orthosteric and allosteric activation of alpha7 nAChR require cooperative activity at the interfa

124 Methyllycaconitine (MLA), an antagonist of alpha7 nAChR, could efficiently block these pathogenic e

125 The simultaneous application of alpha7 nAChR agonist PHA-543613 and PAM NS-1738 resulted

126 ly, electrophysiological characterization of alpha7 nAChR-mediated current traces was similar in term

127 permitted the discovery of a novel class of alpha7 nAChR agonists with improved selectivity, in part

128 The functional coupling of alpha7 nAChR to CFTR occurs through Ca(2+) entry and act

129 losteric site in the extracellular domain of alpha7 nAChR.

130 y investigated and compared local effects of alpha7 nAChR agonist PHA-543613 and PAMs PNU-120596 and

131 Furthermore, effects of alpha7 nAChR antagonist methyllycaconitine (MLA) and GAB

132 ted by RT-PCR and cell surface expression of alpha7 nAChR is detected by confocal microscopy and flow

133 Although the cognitive enhancer potential of alpha7 nAChR agonists and positive allosteric modulators

134 s the pro-cognitive therapeutic potential of alpha7 nAChR agonists.

135 These data identify reduction of alpha7 nAChR function as a potential mechanism for eleva

136 ts demonstrate the anti-inflammatory role of alpha7 nAChR in NK cells and suggest that modulation of

137 This study establishes the potential role of alpha7 nAChR in the regulation of CFTR function and in t

138 dels of BBB were used to dissect the role of alpha7 nAChR in up-regulation of Abeta induced by gp120,

139 identify and develop a distinct scaffold of alpha7 nAChR-selective ligands.

140 t agonists may be able to target a subset of alpha7 nAChR-mediated signaling processes.

141 schizophrenia are evident through the use of alpha7 nAChR agonists, while positive allosteric modulat

142 chizophrenia and also identify activation of alpha7 nAChRs as a potential strategy for tobacco cessat

143 Our findings indicate that activation of alpha7 nAChRs at presynaptic sites, via a mechanism invo

144 ifferences in the mechanism of activation of alpha7 nAChRs by ACh and 4BP-TQS.

145 nificant depressed through the activation of alpha7 nAChRs localized on the TSC and activated by the

146 These data indicate that activation of alpha7 nAChRs was both necessary and sufficient to enhan

147 etermine whether pharmacological blockade of alpha7 nAChRs would increase motivation of rats to intra

148 In the case of alpha7 nAChRs, ACh causes rapid activation and almost co

149 ngly, the main single-channel conductance of alpha7 nAChRs, was significantly larger when activated b

150 Here, we demonstrate that direct coupling of alpha7 nAChRs to G proteins enables a downstream calcium

151 ion, agonist potency, and desensitization of alpha7 nAChRs after exposure to pyrimidine analogues, th

152 rates of smoking, have reduced expression of alpha7 nAChRs and may particularly benefit from this com

153 ey (2004) discovered prominent expression of alpha7 nAChRs in rat SOC, suggesting possible engagement

154 eraging the robust recombinant expression of alpha7 nAChRs with NACHO, we utilized genome-wide cDNA l

155 cells that naturally express high levels of alpha7 nAChRs, such as neurons in the hippocampus and hy

156 unctional, cell- and tissue-specific loss of alpha7 nAChRs by demonstrating that choline-induced alph

157 ent type I positive allosteric modulators of alpha7 nAChRs that may have therapeutic value in restori

158 1b represents the most potent ago-PAM of alpha7 nAChRs available to date and is considered for fu

159 In contrast, stimulation of alpha7 nAChRs by acetylcholine may mediate the increased

160 armacological properties similar to those of alpha7 nAChRs, although amplitudes of alpha7beta2 nAChR-

161 Analysis of alpha7-nAChR function in hippocampal interneurons in cul

162 l regions, supporting higher availability of alpha7-nAChR in MCI.

163 dioligand for estimating the availability of alpha7-nAChR in the brain in vivo with PET.

164 s a potential PET radioligand for imaging of alpha7-nAChR in non-human primates.

165 We also observed that the levels of alpha7-nAChR in human SCC-L tumors (isolated from patien

166 Nicotine increased the levels of alpha7-nAChR mRNA and alpha7-nAChR transcription in huma

167 depends on the second intracellular loop of alpha7-nAChR subunits, and is specific in that it does n

168 ion triggers rapid calcium-dependent loss of alpha7-nAChR clusters.

169 ble imaging properties for quantification of alpha7-nAChR in the human brain.

170 Nicotine-induced up-regulation of alpha7-nAChR required GATA4 and GATA6.

171 Nicotine-induced up-regulation of alpha7-nAChR was confirmed in vivo by chicken chorioalla

172 y, CXCR4 activation induces up-regulation of alpha7-nAChR, causing cell death, suggesting that alpha7

173 nk is required for PMCA2-mediated removal of alpha7-nAChR clusters.

174 Similarly, nicotinic activation of alpha7-nAChRs in WT organotypic culture, as well as cell

175 avioral analysis, we show that activation of alpha7-nAChRs increases in the rat VTA both the tyrosine

176 th impulsivity and locomotor activity and of alpha7-nAChRs in hypothalamic regions associated with ar

177 Blockade of alpha7-nAChRs markedly reduced, whereas low-dose stimula

178 ndogenous PPARalpha ligands are effectors of alpha7-nAChRs and that their neuromodulatory properties

179 ositron emission tomography (PET) imaging of alpha7-nAChRs.

180 such SCC-L patients) causes up-regulation of alpha7-nAChRs, which facilitates tumor growth and progre

181 eptor, induces a functional up-regulation of alpha7-nAChRs.

182 ivity and perhaps functional upregulation of alpha7-nAChRs are necessary for production of Abeta-indu

183 ceptor, its "non-classical" binding sites on alpha7 nAChR should be within the extracellular domain.

184 agonist activity but retain PAM activity on alpha7 nAChRs, demonstrating the importance of the locat

185 led five distinct pharmacological effects on alpha7 nAChRs.

186 dupDeltaalpha7 as well as their influence on alpha7 nAChRs may help explain the pathophysiology of sc

187 ng with the allosteric transmembrane site on alpha7 nAChRs.

188 ylation state of GluA1 which is dependent on alpha7-nAChR and intracellular calcium.

189 explores the effect of nicotine exposure on alpha7-nAChR levels in squamous cell carcinoma of the lu

190 The dependence on alpha7-nAChRs becomes clear when comparing wild-type (WT

191 iral-mediated downregulation of the beta2 or alpha7 nAChR subunit in the amygdala all induced robust

192 e regulated in part by either alpha4beta2 or alpha7 nAChRs.

193 nt may result from perturbed alpha3*- and/or alpha7-nAChR function.

194 pha4beta2-nAChRs, but not on alpha4beta4- or alpha7-nAChRs, suggesting nAChR subunit selectivity of o

195 In addition, nicotine and PNU282987 (alpha7-nAChR agonist) accelerated the growth of the chol

196 Pharmacotherapies potentiating alpha7 nAChR signaling have also been shown to reduce ag

197 bited the effects of nicotine at presynaptic alpha7 nAChRs on glutamate terminals in the mediodorsal

198 Additional immobilization of presynaptic alpha7-nAChRs by antibody crosslinking increases glutama

199 reduction in both protomers almost prevents alpha7 nAChR recognition.

200 8.0) in control mice is superior to previous alpha7-nAChR PET radioligands.

201 f cholangiocarcinoma cell lines and promoted alpha7-nAChR-dependent activation of proliferation and p

202 Rather, alpha7 nAChR activation induced expression of c-Fos and

203 For this reason, alpha7 nAChR agonists represent promising therapeutic ca

204 of alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) is described.

205 ugh Alpha7 nicotinic acetylcholine receptor (alpha7 nAChR).

206 of alpha7 nicotinic acetylcholine receptor (alpha7 nAChR).

207 the alpha7-nicotinic acetylcholine receptor (alpha7-nAChR) in the pathophysiology of Alzheimer's dise

208 the alpha7-nicotinic acetylcholine receptor (alpha7-nAChR) subtype.

209 he alpha-7 nicotinic acetylcholine receptor (alpha7-nAChR), a potential therapeutic target for centra

210 the alpha7 nicotinic acetylcholine receptor (alpha7-nAChR), was more highly expressed in human cholan

211 The alpha7-nicotinic cholinergic receptor (alpha7-nAChR) is a key mediator of brain communication a

212 Alpha-7 nicotinic acetylcholine receptors (alpha7 nAChR) are implicated in the modulation of many c

213 ng alpha7 nicotinic acetylcholine receptors (alpha7 nAChR) may facilitate the specific modulation of

214 th alpha7 nicotinic acetylcholine receptors (alpha7 nAChR) on immunocompetent cells to inhibit cytoki

215 alpha7 Nicotinic acetylcholine receptors (alpha7 nAChR) represent promising therapeutic candidates

216 or alpha7-nicotinic acetylcholine receptors (alpha7-nAChRs) (Ki = 0.4-20 nM) has been synthesized for

217 ontaining nicotinic acetylcholine receptors (alpha7-nAChRs), capable of promoting transmitter release

218 in alpha7 nicotinic acetylcholine receptors (alpha7-nAChRs).

219 sive, or 'serenic,' an effect which requires alpha7 nAChRs and is recapitulated by GTS-21, an alpha7

220 infusion of 0, 10, or 40 nmol of a selective alpha7 nAChR agonist, PNU 282987, into these brain areas

221 nfusions of 0, 10, or 20 pmol of a selective alpha7 nAChR antagonist, alpha-conotoxin ArIB [V11L,V16D

222 ct of long-term treatment with the selective alpha7 nAChR agonist A-582941 in aged 3xTg-AD mice with

223 This effect was blocked by the selective alpha7 nAChR antagonist methyllycaconitine (MLA).

224 ent by nicotine was inhibited by a selective alpha7-nAChR antagonist methyllycaconitine (MLA) and int

225 Since alpha7 nAChRs are present on neurons and glia (including

226 timulated NK cells to PNU-282987, a specific alpha7 nAChR agonist, increases intracellular calcium co

227 Specifically, alpha7-nAChR up-regulation is observed in mouse striatum

228 encoding three requisite receptor subtypes: alpha7-nAChR, alpha4beta2-nAChR, and a serotonin recepto

229 ty receptors (containing the alpha7-subunit, alpha7-nAChRs) can regulate cortical network function ex

230 ime is a species containing alpha7 subunits (alpha7-nAChRs).

231 contain alpha7 nicotinic receptor subunits (alpha7-nAChRs).

232 found that TCR stimulation decreased surface alpha7 nAChRs and reduced single-channel conductance.

233 ed understanding of this novel way to target alpha7 nAChR therapeutically.

234 milar snake alpha-neurotoxins also targeting alpha7 nAChR.

235 We also determined that alpha7 nAChR binding sites were absent on GFAP-positive

236 d from intracellular stores, indicating that alpha7 nAChR is functional.

237 Here, we showed that alpha7 nAChR-dependent calcium signal cascades are downr

238 Our results suggest that alpha7 nAChR PAMs increase neuronal excitability more po

239 ignificantly reduced by MLA, suggesting that alpha7 nAChR may play an important role in neuropatholog

240 Evidence suggests that alpha7 nAChR activation impacts rule acquisition and ini

241 We propose that alpha7 nAChRs coordinate pre- and postsynaptic activitie

242 In recent studies we show that alpha7 nAChRs bind signaling proteins such as heterotrim

243 poly(I:C) stimulation only, indicating that alpha7-nAChR, a highly Ca(2+) permeable ion channel sens

244 We additionally show that alpha7-nAChR stimulation is needed for NMDA actions, sug

245 7-nAChR, causing cell death, suggesting that alpha7-nAChR is a previously unrecognized contributor to

246 tional proteomics on rat brain, we show that alpha7-nAChRs are associated with plasma membrane calciu

247 Here we show that alpha7-nAChRs unexpectedly promote formation of glutamat

248 Our results further suggest that alpha7-nAChRs may buffer ACh and regulate its bioavailab

249 The alpha7 nAChR subtype is highly expressed in the laterodo

250 The alpha7 nAChR-positive allosteric modulator PNU120596 [N-

251 milar to that of alphaCT-alphaCT against the alpha7 nAChR and is more active against alpha3beta2 nACh

252 8A, however, did significantly attenuate the alpha7 nAChR-induced Galphaq calcium signaling response

253 These findings identify the alpha7 nAChR as an important regulator of aggressive beh

254 A mutation of the GPBC in the alpha7 nAChR (alpha7345-348A) abolishes interaction with

255 or different allosteric binding sites in the alpha7 nAChR and paves the way for future development of

256 howed substantially different effects of the alpha7 nAChR agonist and PAMs.

257 nAChR and chimeric receptor composed of the alpha7 nAChR extracellular ligand-binding domain and the

258 nerated mice in which the fourth exon of the alpha7 nAChR gene (Chrna7) is flanked by loxP sites (B6-

259 rophages and supports the involvement of the alpha7 nAChR in regulating the inflammatory response via

260 s that the anti-inflammatory activity of the alpha7 nAChR is mediated by a signal transduction pathwa

261 Lastly we found that the presence of the alpha7 nAChR subtype to both pre- and postsynaptic sites

262 ) a potent and selective full agonist of the alpha7 nAChR that demonstrated improved plasma stability

263 4, WAY-361789), a novel, full agonist of the alpha7 nAChR that was evaluated in vitro and in vivo.

264 ed as potent and selective modulators of the alpha7 nAChR with favorable in vitro safety profiles and

265 mically related allosteric modulators of the alpha7 nAChR.

266 to resemble the ligand-binding domain of the alpha7 nAChR.

267 d provide a new chemical space to target the alpha7 nAChR.

268 Here we show that in contrast to the alpha7 nAChR, the alpha7beta2 nAChR is highly susceptibl

269 to evidence that these PAMs bind within the alpha7 nAChR transmembrane region, we generated and vali

270 suggesting again a presynaptic action of the alpha7 nAChRs.

271 new lead compounds activate selectively the alpha7 nAChRs with EC(50)'s between 30 and 140 nM in a P

272 The alpha7-nAChR selective ligand 1 (SSR180711) blocked the

273 ASEM is an antagonist for the alpha7-nAChR with high binding affinity (Ki = 0.3 nM).

274 thin this series exhibit specificity for the alpha7-nAChR, showing no activation or antagonism of alp

275 T) mice with mice constitutively lacking the alpha7-nAChR gene.

276 confirming a remarkable up-regulation of the alpha7-nAChR in gp120-transgenic mice brains.

277 AChBP showed only two to be agonists on the alpha7-nAChR below 10 muM concentration.

278 the binding of GATA4 or GATA6 to Sp1 on the alpha7-nAChR promoter, thereby inducing its transcriptio

279 compounds in complex mixtures targeting the alpha7-nAChR.

280 RNA interference demonstrates that the alpha7-nAChRs must be expressed in the neuron being inne

281 dings do not support further testing of this alpha7 nAChR PAM compound for possible efficacy in smoki

282 his study suggest that nicotine acts through alpha7-nAChR and plays a novel role in the pathogenesis

283 Thus, alpha7 nAChR agonists appear to be a promising therapeut

284 Thus, alpha7 nAChRs are likely important mediators of the moto

285 Direct activation is sensitive to alpha7 nAChR antagonist methyllycaconitine, although the

286 results also explain why genetic insults to alpha7-nAChR would profoundly disrupt cognitive experien

287 tionally revealed direct binding of Abeta to alpha7-nAChRs and to the Tyr-188 mutant receptor.

288 application data revealed that for wild-type alpha7 nAChR, the 3-furan desensitized state was relativ

289 S) that display similar effects on wild-type alpha7 nAChRs.

290 etylcholine efficacy) at alpha7beta2- versus alpha7-nAChRs.

291 tically depends on cholinergic signaling via alpha7 nAChR.

292 recording all reveal synaptic deficits when alpha7-nAChR input is absent.

293 subsequently examined the hippocampus, where alpha7 nAChRs are highly expressed, particularly in GABA

294 Further, whereas alpha7 nAChR subunit knockdown was somewhat more effecti

295 However, the mechanisms by which alpha7 nAChRs are regulated are poorly understood.

296 gions and potential neural circuits in which alpha7 nAChRs regulate aggressive behavior in male mice.

297 ew homeostatic regulatory mechanism in which alpha7-nAChR restrain may be adjusted as needed at presy

298 , suggesting that longer term treatment with alpha7 nAChR agonists for these deficits in SCZ may be p

299 naptic density-95), which is associated with alpha7-nAChRs and constrains their mobility as revealed

300 18)F-ASEM in the brain regions enriched with alpha7-nAChRs was 80%-90%.