ライフサイエンスコーパス: NMJ

1 NMJ decline occurs in aged animals and may appear before

2 NMJ deficits are aggravated in these mice when compared

3 NMJ formation requires intimate communications among the

4 NMJ formation requires intimate interactions among moton

5 NMJ-in-a-dish models have been developed to examine huma

6 EP domain-dependent, coincides with abnormal NMJ assembly, leading to synaptic degeneration, and, ult

7 FGFBP1 from SOD1(G93A) mice also accelerates NMJ degeneration and death.

8 MP matrices produce more functionally active NMJs-in-a-dish, which could be used to elucidate disease

9 In addition, NMJs of adult transgenic mice that expressed excess axon

10 lie the focal delivery of AChRs to the adult NMJ are not yet understood in detail.

11 a Piccolo-Bassoon-Piccolo structure in adult NMJs.

12 lly ablated SCs during development and after NMJ formation to investigate the consequences of the abl

13 Finally, ablation of SCs at P30, after NMJ maturation, led to NMJ fragmentation and neuromuscul

14 postsynaptic apposition is expanded in aging NMJs, which is accompanied by an expansion of the postsy

15 four striking morphological changes of aging NMJs were revealed.

16 past1 mutants exhibit altered NMJ morphology, decreased synaptic transmission, reduced

17 acetylcholine receptor (AChR) clustering and NMJ (neuromuscular junction) formation.

18 s an E3 ligase to induce AChR clustering and NMJ formation, possibly by regulation of AChR neddylatio

19 dUGP mutants display striking locomotor and NMJ formation defects, including expanded synaptic arbou

20 earch has focused on spinal motor neuron and NMJ aspects of the disease.

21 nd discuss how studies of Drosophila PNS and NMJ development have provided guidance in experimental a

22 ng ALS-like locomotor dysfunction as well as NMJ abnormalities linked to microtubule and synaptic sta

23 f ionotropic glutamate receptors (iGluRs) at NMJ synapses.

24 Synaptic pMad was lost at NMJ synapses developing at suboptimal levels of iGluRs a

25 rt that pMad signals are selectively lost at NMJ synapses with reduced postsynaptic sensitivities.

26 ted, rapsyn fails to associate with AChRs at NMJs of living mice.

27 e experiments define synaptic dysfunction at NMJs experiencing ALS-related degradation and demonstrat

28 we demonstrate critical roles for FGFBP1 at NMJs in developing, aging and SOD1(G93A) mice.

29 growth factor binding protein 1 (FGFBP1) at NMJs.

30 growth factor binding protein 1 (FGFBP1) at NMJs.

31 , alters the rate of loss of motor inputs at NMJs during developmental synapse elimination.

32 aptic arborization and active zone number at NMJs following C9orf72 transgenic expression in motor ne

33 ntial for proper localization of synapsin at NMJs.

34 to maintain proper synaptic transmission at NMJs upon repetitive stimulation, similar to Drp1 fissio

35 t is possible to resolve single motor axons, NMJs and active zones, and perform rapid forward genetic

36 Because NMJ denervation occurs early in the process and that per

37 in skeletal muscles during aging and before NMJ degeneration in SOD1(G93A) mice, a mouse model for a

38 WT mice, before signs of MN death and before NMJ morphological alterations.

39 development, its expression decreases before NMJ degeneration during aging and in SOD1(G93A) mice, a

40 f the C. elegans SMN ortholog, SMN-1, causes NMJ defects.

41 motoneurons and are confined to cholinergic NMJs.

42 ting soft and stiff stripes improves current NMJ-in-a-dish models by inducing both mouse and human my

43 rmation will shed light on whether defective NMJs might contribute to the loss of motor function and

44 ity because they were inserted at denervated NMJs.

45 tic profile (MUSP) that reports MU-dependent NMJ synaptic properties.

46 block, and ligand selectivity for Drosophila NMJ glutamate receptors.

47 amate have been shown to regulate Drosophila NMJ physiology by modulating the clustering of postsynap

48 cally and postsynaptically at the Drosophila NMJ and that it is a presynaptic regulator of rapid acti

49 cterized C9orf72 pathology at the Drosophila NMJ and utilized several approaches to restore synaptic

50 the amplitude of the EPSP at the Drosophila NMJ increases during aging and that the homeostatic sign

51 atively image AP waveforms at the Drosophila NMJ without disrupting baseline synaptic transmission or

52 calibrating Synj function at the Drosophila NMJ, and in turn endocytic capacity, to adapt to conditi

53 naptic signaling machinery at the Drosophila NMJ.

54 Tollo mutants exhibited NMJ undergrowth, whereas increased expression of Tollo l

55 S, FR, and FF NMJs of WT mice showed distinct synaptic properties from

56 In the absence of FGFBP1, NMJs exhibit structural abnormalities in developing and

57 At the fly NMJ, it is believed that the depolarization of the muscl

58 ur data reveal that MuSK CRD is critical for NMJ formation and plays an unsuspected role in NMJ maint

59 the agrin signaling pathway is critical for NMJ maintenance because null mutation of any of the thre

60 ss in a manner that would be detrimental for NMJ repair.

61 indicate that SCs are not only required for NMJ formation, but also necessary for its maintenance; a

62 rp4, two cell surface receptors required for NMJ formation.

63 ynaptic pMad functions as a local sensor for NMJ synapse activity and has the potential to coordinate

64 r transmission at the most highly fragmented NMJs in the diaphragms of old (26-28 months) mice is, if

65 the vector failed to provide protection from NMJ defects despite robust SMN expression in the central

66 muscle fibers, where they formed functional NMJs, restored contractile force.

67 results propose a mechanism whereby further NMJ and skeletal muscle decline ensues upon SC depletion

68 ecruits acetylcholine receptors to GABAergic NMJs.

69 n of the receptor kinase MuSK, which governs NMJ formation, and DOK7 mutations underlie familial limb

70 At the human NMJ, a delay in synaptic maturation and an altered maint

71 However, changes in NMJ properties as a function of MU types remain debated.

72 Defects in NMJ formation during development or maintenance in adult

73 Defects in NMJ transmission cause muscle weakness, termed myastheni

74 Deficits in NMJ formation and maintenance cause neuromuscular disord

75 We review recent findings in NMJ formation, maintenance, neuromuscular disorders, and

76 hysiological role of Wnt-MuSK interaction in NMJ formation and function remains to be elucidated.

77 he implications of the converged pathways in NMJ formation and liver cancer.

78 J formation and plays an unsuspected role in NMJ maintenance in adulthood.

79 adult muscle enabled studies of its role in NMJ maintenance.

80 ized, less is known about the role of SCs in NMJ formation and maintenance.

81 This study reveals a critical role of SCs in NMJ formation as well as maintenance.

82 The role of Schwann cells (SCs) in NMJ formation and maintenance was not well understood.

83 oteins essential for active zone assembly in NMJs, ribbon synapses, and brain synapses.

84 investigated the formation of new boutons in NMJs lacking synapsin [Syn(-)], a synaptic protein impor

85 In contrast, the Piccolo levels in NMJs from aged mice were comparable to levels in adult m

86 eration mechanism of active zone proteins in NMJs from aged mice.

87 on protein levels decreased significantly in NMJs from aged mouse.

88 The underlying hypothesis, that increasing NMJ fragmentation is associated with impaired transmissi

89 ing the structure and function of individual NMJs, we show that neuromuscular transmission at the mos

90 s and localizes to excitatory and inhibitory NMJs, whereas long isoforms are expressed exclusively by

91 o enhance SMN for remodeling aged or injured NMJs.

92 pal LTP deficits and neuromuscular junction (NMJ) abnormalities, characterized by decreased size and

93 n motor neurons, the neuromuscular junction (NMJ) and muscle fibres.

94 itter release at the neuromuscular junction (NMJ) are thought to be removed.

95 The neuromuscular junction (NMJ) consists of a tripartite synapse with a presynaptic

96 eficits, progressive neuromuscular junction (NMJ) denervation and pre-synaptic build-up of mutant Gly

97 ns (MNs) preceded by neuromuscular junction (NMJ) denervation.

98 e reversal of normal neuromuscular junction (NMJ) development where AChR clustering precedes innervat

99 oordinated movement, neuromuscular junction (NMJ) development, synaptic glycosylation, and Wnt trans-

100 protein, leading to neuromuscular junction (NMJ) dysfunction and spinal motor neuron (MN) loss.

101 eptor in muscles for neuromuscular junction (NMJ) formation.

102 ecules orchestrating neuromuscular junction (NMJ) formation.

103 ous system (PNS) and neuromuscular junction (NMJ) have been identified as players in the pathogenesis

104 ts expression at the neuromuscular junction (NMJ) in Drosophila.

105 cells (SCs), at the neuromuscular junction (NMJ) in mice.

106 the pathology of the neuromuscular junction (NMJ) in Pompe disease, reflecting disruption of neuronal

107 ynaptic sites at the neuromuscular junction (NMJ) in vivo remains largely unknown.

108 ctivity; because the neuromuscular junction (NMJ) is a cholinergic synapse, acetylcholine has been as

109 The Drosophila neuromuscular junction (NMJ) is a powerful system for studying synaptic biology,

110 The neuromuscular junction (NMJ) is a synapse between motor neurons and skeletal mus

111 The neuromuscular junction (NMJ) is a synapse formed between motoneurons and skeleta

112 The neuromuscular junction (NMJ) is a tripartite synapse that is formed by motor ner

113 transmission at the neuromuscular junction (NMJ) is an aspect of CMT2D.

114 The Drosophila neuromuscular junction (NMJ) is capable of rapidly budding new presynaptic varic

115 CANCE STATEMENT: The neuromuscular junction (NMJ) is critical for all voluntary movement.

116 The neuromuscular junction (NMJ) is one of the best-studied cholinergic synapses.

117 A hallmark of the neuromuscular junction (NMJ) is the high density of acetylcholine receptors (ACh

118 The neuromuscular junction (NMJ) is the synapse between a motor neuron and skeletal

119 he morphology of the neuromuscular junction (NMJ) is typically affected by neuromuscular disease, whe

120 roles of Mmp at the neuromuscular junction (NMJ) model synapse in the reductionist Drosophila system

121 transmission at the neuromuscular junction (NMJ) of Drosophila, mice, and human.

122 the adult Drosophila neuromuscular junction (NMJ) of ventral abdominal muscles.

123 is of the underlying neuromuscular junction (NMJ) pathology revealed that late-stage delivery of the

124 Denervation of the neuromuscular junction (NMJ) precedes the loss of motor neurons (MNs) in amyotro

125 enorhabditis elegans neuromuscular junction (NMJ) provides a genetically tractable system in which to

126 larval glutamatergic neuromuscular junction (NMJ) represents a powerful synaptic model to investigate

127 and degeneration of neuromuscular junction (NMJ) structure and function occurred in Sod1(-/-) mice b

128 At the glutamatergic neuromuscular junction (NMJ) synapse, we find that Notum secreted from the posts

129 rs at the Drosophila neuromuscular junction (NMJ) through a postsynaptic mechanism.

130 tic apparatus of the neuromuscular junction (NMJ) traps and anchors acetylcholine receptors (AChRs) a

131 TeNT targets the neuromuscular junction (NMJ) with high affinity, yet the nature of the TeNT rece

132 At the Drosophila neuromuscular junction (NMJ), a retrograde BMP signal functions to promote synap

133 he Drosophila larval neuromuscular junction (NMJ), as a potential Repo target gene.

134 he Drosophila larval neuromuscular junction (NMJ), at which glutamate acts as the excitatory neurotra

135 in, a marker for the neuromuscular junction (NMJ), in >50% of the cells.

136 At the neuromuscular junction (NMJ), overexpression of either wild-type or mutant FUS r

137 outons at the larval neuromuscular junction (NMJ), providing a model system to investigate mechanisms

138 at in the Drosophila neuromuscular junction (NMJ), the endocytic scaffolding protein Dap160 colocaliz

139 osine kinase) at the neuromuscular junction (NMJ), thereby preventing fragmentation of the NMJs.

140 ng on the Drosophila neuromuscular junction (NMJ), we find that the AZ cytomatrix (CAZ) is composed o

141 de of the Drosophila neuromuscular junction (NMJ), where it is required for the localisation of corac

142 he Drosophila larval neuromuscular junction (NMJ).

143 rve terminals of the neuromuscular junction (NMJ).

144 melanogaster larval neuromuscular junction (NMJ).

145 ive weakening of the neuromuscular junction (NMJ).

146 of the fully mature neuromuscular junction (NMJ).

147 melanogaster larval neuromuscular junction (NMJ).

148 is at the Drosophila neuromuscular junction (NMJ).

149 nts of the mammalian neuromuscular junction (NMJ).

150 usion at presynaptic neuromuscular junction (NMJ).

151 MP) signaling at the neuromuscular junction (NMJ).

152 tion, neuromuscular [neuromuscular junction (NMJ)] abnormalities, and axonal death were investigated

153 show that at larval neuromuscular junctions (NMJ), motor neuron expression of wild-type human PFN1 in

154 ALS are seen in the neuromuscular junctions (NMJs) and lower motor neurons, and selective reduction o

155 Neuromuscular junctions (NMJs) are critical for survival and daily functioning.

156 zones in mammalian neuromuscular junctions (NMJs) at sub-diffraction limited resolution remains unkn

157 mammals age, their neuromuscular junctions (NMJs) gradually change their form, acquiring an increasi

158 orted morphology of neuromuscular junctions (NMJs) in patients suffering from epidermolysis bullosa s

159 udy we used the CM9 neuromuscular junctions (NMJs) in the adult Drosophila to investigate the stabili

160 ical alterations at neuromuscular junctions (NMJs) of the diaphragm and tibialis anterior muscle as p

161 wann cells (SCs) at neuromuscular junctions (NMJs) play active roles in synaptic homeostasis and repa

162 and maintenance of neuromuscular junctions (NMJs) remains largely unknown.

163 ture and functional neuromuscular junctions (NMJs) when cocultured with chick myofibers for several w

164 d their output, the neuromuscular junctions (NMJs), has been considered a key factor in the detriment

165 previously damaged neuromuscular junctions (NMJs), suggesting that the beneficial effects of iMuSCs

166 mbryonic Drosophila neuromuscular junctions (NMJs), where low-frequency Ca(2+) oscillations are requi

167 rom degeneration of neuromuscular junctions (NMJs), which form the connection between MNs and muscle

168 ound defects of the neuromuscular junctions (NMJs).

169 otor innervation at neuromuscular junctions (NMJs).

170 axonal inputs from neuromuscular junctions (NMJs).

171 newly reinnervated neuromuscular junctions (NMJs).

172 of mitochondria in neuromuscular junctions (NMJs).

173 Syt4 at Drosophila neuromuscular junctions (NMJs).

174 ured with MNs, were able to form even larger NMJs.

175 ipts involved in establishing or maintaining NMJ structure.

176 The ability to regenerate the mature NMJ in aged or injured SMN-depleted mice was grossly imp

177 arget of the SMN protein and that mitigating NMJ defects may be one strategy in treating human spinal

178 otransmitter release magnitude at LEMS model NMJs.

179 se in neurotransmitter release at LEMS model NMJs.

180 intact, likely operate suboptimally at most NMJs of CMT2D mice.

181 regulating synapse elimination at the mouse NMJ, where loss of a single glial cell protein, the glia

182 ecular architecture of active zones in mouse NMJs at sub-diffraction limited resolution, and describe

183 localization of these two proteins in mouse NMJs revealed using dual-color stimulated emission deple

184 Mutant NMJ showed reduced surface areas and lower volumes of pr

185 ed in the postsynaptic compartment of mutant NMJs include reduced glutamate receptor field size, and

186 duction of release at a proportion of mutant NMJs.

187 Smaller mutant NMJs with correspondingly fewer vesicles and partial den

188 We observed a normal NMJ organization at a presymptomatic stage of ALS (120 d

189 s study was to examine how the alteration of NMJ physiology contributes to Pompe disease pathology; w

190 physiological, and histochemical analyses of NMJ-related measures of the tibialis anterior muscles of

191 We analyzed expression of NMJ-related genes, in situ muscle force production, and

192 mechanism involving at least the failure of NMJ function, activation of proteosome degradation, and

193 asticity, a fundamental and adaptive form of NMJ plasticity in which perturbation to postsynaptic neu

194 ntial component required for the function of NMJ glutamate receptors, permitting analysis of glutamat

195 Despite the importance of NMJ denervation in ALS, the mechanisms involved remain u

196 Our data suggest the loss of NMJ integrity is a primary contributor to the decline in

197 both muscle prepatterning, the first step of NMJ formation, and synapse differentiation associated wi

198 Quantal analysis of NMJs in two different mouse models of CMT2D (Gars(P278KY

199 ession of TDP-43(Q331K) caused dying-back of NMJs and axons, which could not be suppressed by mutatio

200 ic transmission and morphological changes of NMJs have been explored in two nerve-muscle preparations

201 ing age- and disease-related degeneration of NMJs.

202 ion of ventral root axons and denervation of NMJs.

203 uman DOK7 gene resulted in an enlargement of NMJs and substantial increases in muscle strength and li

204 therapy likewise resulted in enlargement of NMJs as well as positive effects on motor activity and l

205 n contributes to the structural integrity of NMJs by linking them to the postsynaptic intermediate fi

206 and maintaining the structural integrity of NMJs.

207 tion to maintain the structural integrity of NMJs.

208 of spinal motor neurons, and maintenance of NMJs.

209 ssociation with the postsynaptic membrane of NMJs.

210 s this gap in information, the morphology of NMJs was examined in two mouse models of SBMA, a myogeni

211 The observed pathology of NMJs in diseased SBMA mice is likely the morphological c

212 logical analysis revealed two populations of NMJs in partially denervated Hb9(cre)NCAM(flx) soleus mu

213 udied how SCs contribute to reinnervation of NMJs using vital imaging of mice whose motor axons and S

214 sential role of iMuSCs in the restoration of NMJs related to injuries and diseases.

215 The ultrastructure of NMJs revealed additional pathology, including deficits i

216 we examined the impact of deleting FGFBP1 on NMJs.

217 d maintenance of AChR clusters, postsynaptic NMJ organization, and body locomotion.

218 atory or inhibitory identity of postsynaptic NMJ domains.

219 that developmental BMP signaling potentiates NMJs for rapid activity-dependent structural plasticity

220 evolve with disease progression but precede NMJ neurodegeneration.

221 ression in neurons is sufficient to preserve NMJ and skeletal muscle structure and function in Sod1(-

222 ease was necessary and sufficient to promote NMJ growth.

223 ss of function of these mutants in promoting NMJ remodeling.

224 ades of study, the inability to reconstitute NMJ glutamate receptor function using heterologous expre

225 effective in modifying parameters reflecting NMJ structure and function nor in force restoration desp

226 and post-synaptic morphology at regenerating NMJs.

227 lysis revealed SC activity near regenerating NMJs.

228 hese data demonstrate that FUS/Caz regulates NMJ development and plays an evolutionarily conserved ro

229 both necessary and sufficient for regulating NMJ growth.

230 vidence that PFN1 is important in regulating NMJ morphology and influences survival and locomotion in

231 the glycogen synthase kinase-3, that rescued NMJ defects in MuSKDeltaCRD mice and therefore constitut

232 At postnatal day 180 (P180), FF and S NMJs of SOD1 already showed, respectively, lower and hig

233 s of congenital myasthenia, including severe NMJs dismantlement, muscle weakness, and fatigability.

234 neuromuscular disease characterized by small NMJs.

235 timulation, and (4) release failures at some NMJs with high-frequency, long-duration stimulation.

236 entiated neurotransmission at newly sprouted NMJs, while chronic intraperitoneal treatment with nifed

237 found that budding of new boutons at Syn(-) NMJs was significantly diminished, and that new boutons

238 uscle fiber size, enhances the post-synaptic NMJ area, reduces the abnormal accumulation of intermedi

239 We hypothesized that NMJ synaptic functions would be altered precociously in

240 We suggest that NMJ fragmentation per se is not a reliable indicator of

241 The NMJ had significant levels of activated caspase-3 but li

242 he synapse, where it either moves across the NMJ into the postsynaptic muscle cell or induces PrP(Sc)

243 PrP(Sc) formation on muscle cells across the NMJ.

244 whereas application of exogenous NMDA at the NMJ accelerates synapse elimination and increases muscle

245 elay in postnatal synapse elimination at the NMJ across all muscle groups examined.

246 phosphorylation regulates MT capture at the NMJ and how this controls the size of AChR clusters are

247 significant reduction of futsch mRNA at the NMJ compared with motor neuron cell bodies where we find

248 drugs which improve synaptic efficacy at the NMJ could be considered in treating the pathophysiology

249 During the period of denervation, SCs at the NMJ extend elaborate processes from the junction, as sho

250 these findings, knockdown of LL5beta at the NMJ in vivo reduces the density and insertion of AChRs i

251 s believed that homeostatic signaling at the NMJ is bi-directional and considerable progress has been

252 of nidogens (also known as entactins) at the NMJ is the main determinant for TeNT binding.

253 and receptor density of AChR clusters at the NMJ through the delivery of AChRs and that this is regul

254 ChE) and butyrylcholinesterase (BChE) at the NMJ to bring out the function of different ACh receptors

255 and that local glial cells secrete Wg at the NMJ to regulate glutamate receptor clustering and synapt

256 However, a conundrum persists at the NMJ whereby persistent but incoherent opposite neurotran

257 matrix protein as a receptor for TeNT at the NMJ, paving the way for the development of therapeutics

258 tic Schwann cells (PSCs), glial cells at the NMJ, regulate morphological stability, integrity, and re

259 ed cells exhibited PrP(Sc) deposition at the NMJ, suggesting additional prion replication and dissemi

260 other proteins involved in processes at the NMJ, which would be consistent with the previous observa

261 BMP receptor-containing compartments at the NMJ.

262 observation that CK2 appears enriched at the NMJ.

263 Tollo signals through the JNK pathway at the NMJ.

264 eduction in Futsch protein expression at the NMJ.

265 extrasynaptic sensor for homeostasis at the NMJ.

266 lutamate receptors are also expressed at the NMJ.

267 uggest that therapies aimed at enlarging the NMJ may be useful for a range of neuromuscular disorders

268 se mutation on mRNA levels and evaluated the NMJ transmission in VAMP1(lew/lew) mice, observing neuro

269 e structural and functional integrity of the NMJ and that loss of muscle LRP4 in adulthood alone is s

270 ts demonstrate that relative maturity of the NMJ determines the temporal requirement for the SMN prot

271 The postsynaptic apparatus of the NMJ is organized by agrin secreted from motor neurons.

272 mbrane infoldings and disorganization of the NMJ microenvironment, including its invasion by microtub

273 ng a protein involved in organization of the NMJ, and emphasize the importance of appropriate symptom

274 e, neuromuscular disorders, and aging of the NMJ, focusing on communications among motoneurons, muscl

275 ical stability, integrity, and repair of the NMJ, one could predict that PSC functions would be alter

276 junction with histological assessment of the NMJ.

277 XIII in the formation and maintenance of the NMJ.

278 grin-known to be a critical organizer of the NMJ.

279 the developmentally regulated growth of the NMJ.

280 S and potentially for other disorders of the NMJ.

281 manner, before structural alterations of the NMJ.

282 that similar mechanisms target mRNAs to the NMJ and the oocyte posterior.

283 e of AChRs in the targeting of rapsyn to the NMJ in vivo SIGNIFICANCE STATEMENT: Rapsyn is required f

284 In contrast to the NMJ, PrP(Sc) was not associated with synaptophysin in ne

285 The NMJs of staufen mutant larvae have also a reduced number

286 e impairment of synaptic transmission at the NMJs.

287 MJ), thereby preventing fragmentation of the NMJs.

288 ce lacking the FE65/FE65L1 binding site, the NMJs of APLP2/FE65-DKO and APLP2/FE65L1-DKO mice were an

289 As their NMJ deficits resemble those of mutant APP/APLP2-DKO mice

290 (TGF-beta1) in skeletal muscles and at their NMJs.

291 pairments of PSC functions may contribute to NMJ dysfunction and ALS pathogenesis.

292 Multiple mechanisms contribute to NMJ repair and maintenance; however muscle stem cells (s

293 red even before denervation, contributing to NMJ malfunctions.

294 f SC studies to attenuate muscle loss due to NMJ deterioration as observed in neuromuscular diseases

295 However, unlike Drp1, loss of Marf leads to NMJ morphology defects and extended larval lifespan.

296 of SCs at P30, after NMJ maturation, led to NMJ fragmentation and neuromuscular transmission deficit

297 whereas increased expression of Tollo led to NMJ overgrowth.

298 y affected by neuromuscular disease, whether NMJs in SBMA are similarly affected by disease is not kn

299 een identified ten proteins co-evolving with NMJ glutamate receptors.

300 cantly larger than the response at the young NMJ, appropriate for a synapse at which the set point ha