ライフサイエンスコーパス: gamma-secretase

1 sor protein (APP) via cleavages by beta- and gamma-secretase.

2 a (PEA15), and its mRNA are regulated by PS1/gamma-secretase.

3 sequential proteolytic cleavage by BACE1 and gamma-secretase.

4 r protein (APP) by beta-secretase (BACE) and gamma-secretase.

5 beta-site APP cleaving enzyme 1 (BACE1) and gamma-secretase.

6 M, where it is normally processed rapidly by gamma-secretase.

7 ation of hair cells induced by inhibition of gamma-secretase.

8 PP) by beta-secretase 1 (BACE-1) followed by gamma-secretase.

9 that affect the proteolytic activity of the gamma-secretase.

10 n presenilin 1 (PS1), a catalytic subunit of gamma-secretase.

11 y a disintegrin and metalloproteinase 10 and gamma-secretase.

12 DAM10 and the downstream S3 cleavage enzyme, gamma-secretase.

13 ping molecular imaging tools for visualizing gamma-secretase.

14 ion, suggesting a functional conservation of gamma-secretase.

15 ar domain requires the enzymatic activity of gamma-secretase.

16 re required for stoichiometric inhibition of gamma-secretase.

17 ment, a region containing the active site of gamma-secretase.

18 al change contributing to the specificity of gamma-secretase.

19 loid precursor protein (APP) by the beta and gamma secretases.

20 amyloid precursor protein (APP) by beta- and gamma-secretases.

21 protease complex containing active beta- and gamma-secretases.

22 2 (PS1 and 2) are the catalytic subunits of gamma-secretase, a multiprotein protease that cleaves am

23 lize in lipid raft fractions, with increased gamma-secretase accumulation upon CRF treatment.

24 PS1/gamma-secretase activates the transcription factor, cAMP

25 The mechanism by which gamma-secretase activating protein (GSAP) regulates gamm

26 Here we show that the gamma-secretase activating protein (GSAP), a key enzyme

27 e gamma-secretase complex and its activator, gamma-secretase activating protein (GSAP).

28 We find residual carboxy- and endo-peptidase gamma-secretase activities, similar to the formerly char

29 Furthermore, membralin deficiency enhances gamma-secretase activity and neuronal degeneration.

30 Furthermore, knockout of IFITM3 reduces gamma-secretase activity and the formation of amyloid pl

31 as further validated by a fluorescence-based gamma-secretase activity assay, which confirmed inhibiti

32 nhibitor X (Inh X), a compound that inhibits gamma-secretase activity before exposing to MAG or CNS m

33 t of GSAP in cultured cells directly reduces gamma-secretase activity for Abeta production, but not f

34 cells under serum withdrawal, while blocking gamma-secretase activity had no effect.

35 ecretase activating protein (GSAP) regulates gamma-secretase activity has not yet been elucidated.

36 ctivity assay, which confirmed inhibition of gamma-secretase activity in NMK-T-057-treated BC cells.

37 x has a strong and positive correlation with gamma-secretase activity in samples from patients with l

38 h the mutation of the proposed pivot rescues gamma-secretase activity inNCT-deficient cells in a mann

39 vious reports, we and others have shown that gamma-secretase activity is enriched in mitochondria-ass

40 Modulation of gamma-secretase activity to reduce toxic amyloid-beta pe

41 (PSEN1) mutations lead to either (2) reduced gamma-secretase activity, (3) altered protein stability

42 phorylation of PS1 at Ser367 does not affect gamma-secretase activity, but has a dramatic effect on A

43 ations cause loss of Presenilin function and gamma-secretase activity, including impaired Abeta produ

44 in the absence of presenilin expression and gamma-secretase activity, TNF-mediated JNK activation wa

45 rats survive into adulthood despite loss of gamma-secretase activity.

46 Abeta levels through indirect inhibition of gamma-secretase activity.

47 solic side of TMD4 affect Abeta42-generating gamma-secretase activity.

48 ptide that can be shown to directly modulate gamma-secretase activity.

49 nset Alzheimer's disease that exhibit higher gamma-secretase activity.

50 9), when delivered to the ER for cleavage by gamma-secretase, acts as a lipid-sensing peptide that fo

51 Inhibition of gamma-secretase also decreases neuronal survival under G

52 esenilin 1 (PS1) is the catalytic subunit of gamma-secretase, an enzyme complex responsible for the m

53 These observations implicate gamma-secretase and its mediated neurodevelopmental path

54 Inhibition of gamma-secretase and metalloproteinase proteolysis in the

55 Pharmacological inhibition of gamma-secretase and NOTCH1 processing also abrogates SKB

56 -based compounds for their potential to bind gamma-secretase and observed that 3-(3'4',5'-trimethoxyp

57 mbrane platform enabling characterization of gamma-secretase and substrate within proteolipobead asse

58 first step for the subsequent processing by gamma-secretase and the release of gene regulatory intra

59 M3 in neurons and astrocytes, which binds to gamma-secretase and upregulates its activity, thereby in

60 t (HMW) complex (~5 MD) containing beta- and gamma-secretases and holo-APP was catalytically active i

61 s sequentially cleaved by alpha-, beta-, and gamma-secretase, and the released CX3CL1 intracellular d

62 ) fragment that reverses axon defects in PS1/gamma-secretase- and EphA3-deficient hippocampal neurons

63 gamma-Secretases are a family of intramembrane-cleaving

64 id is not an essential element necessary for gamma-secretase assembly, activity, and stability, and t

65 e lid deletion has any significant impact on gamma-secretase assembly, activity, and stability, and t

66 ent cells, and then assessed their impact on gamma-secretase assembly, activity, and stability.

67 We visualized gamma-secretase association with substrates like amyloid

68 e type 1-oriented stub is further cleaved by gamma-secretase at an -like site five amino acids N-term

69 reover, it affects the cleavage precision of gamma-secretase at the gamma-site similar to certain Alz

70 n suggest that the enzymatic function of PS1/gamma-secretase can be modulated by its 'phosphorylated'

71 PSEN1 maturation, all culminating in reduced gamma-secretase carboxypeptidase-like activity.

72 ain -named JCasp- is naturally produced by a gamma-secretase/caspase double-cut of APP.

73 Herein, we demonstrate that gamma-secretase catalysis is driven by the stabilization

74 o address the frequency of susceptibility to gamma-secretase cleavage among human RTKs.

75 Both mutants impaired gamma-secretase cleavage and also altered its cleavage s

76 lf-renewal upon proteolytic activation via a gamma-secretase cleavage complex (PS1, PS2) and TACE (AD

77 Another protein that undergoes very similar gamma-secretase cleavage is the p75 neurotrophin recepto

78 S1 FAD mutants decrease the EphB4-stimulated gamma-secretase cleavage of ephrinB2 and reduce producti

79 dy that detects the neo-epitope created upon gamma-secretase cleavage of NOTCH3 to release its intrac

80 degradation of the mutant APP, and inhibited gamma-secretase cleavage of the mutant C99 to generate A

81 degradation of the mutant APP, and inhibited gamma-secretase cleavage of the mutant C99 to generate a

82 a gamma-secretase substrate and suggest that gamma-secretase cleavage of TNFR1 represents a new layer

83 nal fragment is a prerequisite for efficient gamma-secretase cleavage of TNFR1.

84 (1) APP V717I mutations alter gamma-secretase cleavage site preference.

85 Because this residue is just before the gamma-secretase cleavage site, we then investigated whet

86 weak hydrogen bonds are at or near preferred gamma-secretase cleavage sites, suggesting that the sequ

87 into recipient cells, and upon activation by gamma-secretase cleavage, induces NOTCH-specific gene ex

88 xibility of this hinge might be critical for gamma-secretase cleavage, we mutated one of the glycine

89 e TAM family members AXL or TYRO3 depends on gamma-secretase cleavage.

90 It reduces both the beta-secretase and gamma-secretase cleavages of the amyloid precursor prote

91 es, besides the canonical alpha-, beta-, and gamma-secretases, cleave the amyloid precursor protein (

92 Additionally, CRFR1 and gamma-secretase co-localize in lipid raft fractions, wit

93 ation of Abeta is directly controlled by the gamma-secretase complex and its activator, gamma-secreta

94 mature form and impairs the integrity of the gamma-secretase complex as well as its catalytic activit

95 Understanding of the structure of the gamma-secretase complex consisting of presenilin (PS), a

96 Whether the composition of a given gamma-secretase complex determines a specific cellular t

97 own that presenilins (PS), components of the gamma-secretase complex frequently mutated in familial A

98 The amount of IFITM3 in the gamma-secretase complex has a strong and positive correl

99 2/40 peptide ratio generated by the HMW beta/gamma-secretase complex indistinguishably from that obse

100 erated from intramembraneous cleavage by the gamma-secretase complex is not well defined.

101 f transmembrane substrates by the presenilin-gamma-secretase complex is preceded and regulated by she

102 The gamma-secretase complex is responsible for the cleavage

103 uttle Notch1 and Rheb esRNA and component of gamma-secretase complex presenilin 1 from Tsc1-null cell

104 a-CTF) from the Abeta precursor protein, the gamma-secretase complex produces the Abeta peptides asso

105 ptors, their ligands (Jagged 1-2, DLL1,3,4), gamma-secretase complex proteins (Presenilin 1, Nicastri

106 whose protein products partially compose the gamma-secretase complex that cleaves Abeta from amyloid

107 ansmembrane peptidomimetic inhibitors of the gamma-secretase complex that contain an N-terminal helic

108 e protein nicastrin (NCSTN), a member of the gamma-secretase complex that functions to recruit substr

109 Abeta is generated from holo-APP by a BACE1-gamma-secretase complex that provides sequential, effici

110 e identify nicastrin, a key component of the gamma-secretase complex, as a membralin binding protein

111 enilin 1 (PS1), the catalytic subunit of the gamma-secretase complex, cleaves betaCTF to produce Abet

112 then by the Presenilin 1 (PS1) enzyme in the gamma-secretase complex, generating Abeta.

113 and should allow visualization of the active gamma-secretase complex, poised for intramembrane proteo

114 and subsequent enzymatic proteolysis by the gamma-secretase complex, resulting in the cytoplasmic re

115 s known role as the catalytic subunit of the gamma-secretase complex, selective phosphorylation of PS

116 s known role as the catalytic subunit of the gamma-secretase complex, selective phosphorylation of PS

117 mpound (also known as NMK-T-057) can bind to gamma-secretase complex.

118 membrane proteolysis of p75 catalyzed by the gamma-secretase complex.

119 a-site APP-cleaving enzyme 1 (BACE1) and the gamma-secretase complex.

120 have been found in three genes encoding the gamma-secretase complex: nicastrin (NCSTN), presenilin 1

121 gamma-Secretase complexes (GSECs) are multimeric membran

122 gamma-Secretase complexes achieve the production of amyl

123 termine whether the cellular distribution of gamma-secretase complexes contributes to substrate selec

124 asmids allow for the formation of functional gamma-secretase complexes displaying specific activities

125 ive scissile bond choices by tissue-specific gamma-secretase complexes following the intracellular do

126 We show that PS1-containing gamma-secretase complexes were targeted to the plasma me

127 ured illumination microscopy revealed single gamma-secretase complexes with a monodisperse distributi

128 Cells co-express differing gamma-secretase complexes, including two homologous pres

129 resenilin-dependent subcellular targeting of gamma-secretase complexes.

130 grin and metalloprotease 10 (ADAM10) and the gamma-secretase component presenilin-1.

131 Presenilin 1 (PS1) is an essential gamma-secretase component, the enzyme responsible for am

132 served dependence of C99 protein cleavage by gamma-secretase, critical to the formation of amyloid-be

133 Recent determination of intact human gamma-secretase cryo-electron microscopy structure has o

134 PS1/gamma-secretase-deficient neurons show decreased phospho

135 The final cleavage is gamma-secretase dependent and releases the active Notch

136 We provide evidence that gamma-secretase-dependent but RBPj-independent Notch int

137 The DSCAM ICD is released by gamma-secretase-dependent cleavage, and both the DSCAM a

138 In conclusion, PS/gamma-secretase-dependent EphA3 cleavage mediates axon g

139 r differentiation during development through gamma-secretase-dependent intramembrane proteolysis foll

140 at excess GH activates Notch1 signaling in a gamma-secretase-dependent manner.

141 rat SC migration and induces their death via gamma-secretase-dependent regulated intramembrane proteo

142 Thus, localization of gamma-secretases determines substrate specificity, while

143 super-resolution microscopy for the study of gamma-secretase distribution and dynamics in the membran

144 lease of soluble BCMA (sBCMA); inhibition of gamma-secretase enhanced surface expression of BCMA and

145 acaques shared certain brain areas with high gamma-secretase expression, suggesting a functional cons

146 infectivity in vitro SPP is a member of the gamma-secretase family, and mice lacking SPP are embryon

147 Moreover, inhibition of gamma-secretase following APP accumulation in the TGN in

148 nistically, AIBP triggered relocalization of gamma-secretase from lipid rafts to nonlipid rafts where

149 Impaired gamma-secretase function is associated with the developm

150 Consistent with loss of gamma-secretase function, Psen1(LF/LF) rats exhibited lo

151 be a prerequisite for substrate binding and gamma-secretase function.

152 in and metalloproteinase (ADAM) proteins and gamma-secretase generates intracellular C-terminal fragm

153 cell surface by the ubiquitous multisubunit gamma-secretase (GS) complex, which reduces ligand densi

154 their effect on the physiologic functions of gamma-secretase has not been tested in human model syste

155 coimmunoprecipitated and cofractionated with gamma-secretase in cultured cells and in mouse and human

156 , suggesting a novel direct role for PS1 and gamma-secretase in mitochondrial stress.

157 t mice defective of the nicastrin subunit of gamma-secretase in oligodendrocytes have hypomyelination

158 priate kinetics and distribution for imaging gamma-secretase in the brain.

159 amyloid precursor protein (APP) cleavage by gamma-secretase, increasing the proportion of longer amy

160 These data uncover a ligand-dependent, but gamma-secretase-independent, non-canonical Notch signali

161 ssion and reduced Notch signaling, either by gamma-secretase inhibition or loss of Dll4, rescue retin

162 armacologic blockage of Notch activation via gamma-secretase inhibition.

163 but prevented by combined chemical beta and gamma-secretase inhibition.

164 ADAM10 inhibitor (GI254023X) and gamma-secretase inhibitor (DAPT) were used to inhibit CD

165 stigated the combination between miR-34a and gamma-secretase inhibitor (gammaSI), Sirtinol or zoledro

166 d resistant CCA cell lines pretreated with a gamma-secretase inhibitor (GSi) cocktail demonstrated th

167 ebrile Th2 switch was IL4 independent, but a gamma-secretase inhibitor abrogated it, and it was not f

168 Blocking Notch receptor activation with the gamma-secretase inhibitor DAPT (N-[N-(3,5-difluorophenac

169 Pharmacological inhibition of Notch1 by gamma-secretase inhibitor DAPT (N-[N-(3,5-Difluorophenac

170 Using gamma-secretase inhibitor DAPT to acutely block canonica

171 lidate a protocol that utilizes BMP4 and the gamma-secretase inhibitor DAPT to induce SE differentiat

172 promote neuronal differentiation such as the gamma-secretase inhibitor DAPT.

173 vels, and chronic Notch blockade through the gamma-secretase inhibitor dibenzazepine down-regulated L

174 Treatment of mice with the gamma-secretase inhibitor dibenzazepine to diminish Notc

175 ne tissues from mice given injections of the gamma-secretase inhibitor dibenzazepine, and mice with i

176 ombined with intrahippocampal injection of a gamma-secretase inhibitor evaluates the impact of Abeta

177 disruption of HUVEC-based tube formation by gamma-secretase inhibitor L1790 confirmed the critical r

178 Treatment with the gamma-secretase inhibitor LY3039478 led to inhibition of

179 These effects were suppressed by the gamma-secretase inhibitor LY450139.

180 jective response rate after therapy with the gamma-secretase inhibitor PF-03084014 in patients with r

181 ing Ab or specific inhibition of Notch1 by a gamma-secretase inhibitor substantially inhibits LFA-1/I

182 ages from CSL/RBP-Jkappa KO mice phenocopied gamma-secretase inhibitor treatment for reduced IL-12p40

183 ry cortical neurons, and can be prevented by gamma-secretase inhibitor treatment.

184 dent protein kinase (PKG) inhibitor, but not gamma-secretase inhibitor, abolished the elevation of sy

185 Treatment with the gamma-secretase inhibitor, DAPT, to inhibit cleavage and

186 nyl]-S-phenylglucine t-butyl ester (DAPT), a gamma-secretase inhibitor, which inhibits Notch signalin

187 minutes of blocking Abeta production with a gamma-secretase inhibitor.

188 Inhibition of the Notch pathway by the gamma-secretase inhibitorN-[N-(3,5-difluorophenacetyl)-l

189 Gamma-secretase inhibitors (GSI) and anti-Notch4 were al

190 Targeting glioblastoma stem cells with gamma-secretase inhibitors (GSIs) disrupts the Notch pat

191 However, inhibition of NOTCH signaling with gamma-secretase inhibitors (GSIs) has shown limited anti

192 nds and receptors, as well as small-molecule gamma-secretase inhibitors (GSIs), have been developed t

193 We have recently reported that clinical gamma-secretase inhibitors (GSIs), initially developed t

194 In search of novel gamma-secretase inhibitors (GSIs), we screened a series

195 astic leukemia (T-ALL) and Notch inhibitors (gamma-secretase inhibitors [GSIs]) have produced respons

196 Together, with the use of gamma-secretase inhibitors and scRNA-Seq, confirms that

197 gamma-secretase inhibitors are commonly used to probe NO

198 udies highlight the potential application of gamma-secretase inhibitors as a therapeutic target in pe

199 ependent on secretase activity as ADAM10 and gamma-secretase inhibitors blocked RAGE ligand-mediated

200 f systemic Notch blockade were observed with gamma-secretase inhibitors in preclinical and early clin

201 MPTP opening was directly regulated by gamma-secretase inhibitors independent on organelle calc

202 of novel therapies, including nelarabine and gamma-secretase inhibitors, in adult patients with T-cel

203 The absence or reduction of PS1, as well as gamma-secretase inhibitors, increases neuronal miR-212,

204 se methods, the most common of which are the gamma-secretase inhibitors, which produce a pan-Notch in

205 gh track-density areas that are sensitive to gamma-secretase inhibitors.

206 We asked whether beta- and gamma-secretases interact to mediate efficient sequentia

207 F [99-residue CTF (C99)]- and Notch-specific gamma-secretase interaction assays identified a unique E

208 ge of the amyloid precursor protein (APP) by gamma-secretase is a crucial first step in the evolution

209 gamma-secretase is a macromolecular complex that catalyz

210 gamma-Secretase is a membrane-embedded aspartyl protease

211 gamma-Secretase is a multi-subunit enzyme whose aberrant

212 gamma-Secretase is a prime drug target for AD; however,

213 a fibrils implicated in Alzheimer's disease, gamma-secretase is an important target for developing th

214 gamma-secretase is an intramembrane protease complex tha

215 gamma-Secretase is an intramembrane-cleaving protease th

216 gamma-Secretase is an intramembrane-cleaving protease th

217 gamma-Secretase is an intramembranous protein complex co

218 gamma-secretase is composed of four subunits: nicastrin

219 a-amyloid precursor protein C99 substrate by gamma-secretase is implicated in Alzheimer's disease pat

220 These findings reveal a mechanism in which gamma-secretase is modulated by neuroinflammation via IF

221 We show that presenilin-1 (PS1)/gamma-secretase is required for axon growth in the devel

222 gamma-secretase is responsible for the proteolysis of am

223 teolysis by the canonical alpha-, beta-, and gamma-secretases is simplistic, with the discovery of a

224 ing and subsequent intramembrane cleavage by gamma-secretase leads to release of a soluble intracellu

225 f APP by beta secretase 1 enzyme (BACE1) and gamma-secretase leads to the production and release of A

226 dulating amyloid precursor protein (APP) and gamma-secretase levels in lipid rafts.

227 While its structure is atomically resolved, gamma-secretase localization in the membrane in situ rel

228 milder phenotype than either global Notch or gamma-secretase loss.

229 In living cells, sptPALM revealed PSEN1/gamma-secretase mainly with directed motility and freque

230 autophagy-mediated cell death by inhibiting gamma-secretase-mediated activation of Notch signaling.

231 Taken together, these data indicate that gamma-secretase-mediated cleavage provides an additional

232 PS1/gamma-secretase mediates axon growth by inhibiting RhoA

233 Hence, pharmacological inhibition of gamma-secretase might lead to the subsequent inhibition

234 rsity of observed NOTCH receptor engagement, gamma-secretase modulation was rationalized as a therape

235 Starting from RO6800020 (1), our former gamma-secretase modulator (GSM) lead compound, we utiliz

236 The synthesis of the gamma-secretase modulator MK-8428 (1) is described.

237 he industry is now on the cusp of delivering gamma secretase modulators for clinical proof-of-mechani

238 uation of a novel series of oxadiazine-based gamma secretase modulators obtained via isosteric amide

239 We used our recently developed gamma-secretase modulators (GSMs) and synthesized our GS

240 e disclose three structurally differentiated gamma-secretase modulators (GSMs) based on an oxadiazine

241 icient synthesis of pyridopyrazine-1,6-dione gamma-secretase modulators (GSMs) is described.

242 icant therapeutic interest for the design of gamma-secretase modulators for Alzheimer disease.

243 gamma-Secretase modulators, a class of Alzheimer's disea

244 The isolated complex responded properly to gamma-secretase modulators.

245 nduced transmembrane protein 3 (IFITM3) as a gamma-secretase modulatory protein, and establish a mech

246 through novel mechanisms shared with neither gamma-secretase nor PS2.

247 cells was neither modified by inhibition of gamma-secretase, nor by ER calcium retention.

248 est that combinatorial actions of ADAM10 and gamma-secretase on SIRPalpha cleavage promote inflammato

249 nd SGSMs on both endogenous Abeta levels and gamma-secretase physiologic functions including endogeno

250 lignancies, including breast, and the enzyme gamma-secretase plays an important role in the activatio

251 ctive site, providing the mechanism by which gamma-secretase preferentially cleaves APP in three amin

252 ILEI has been seen to interact with the gamma-secretase presenilin 1 subunit (PS1).

253 Druggability simulations show that gamma-secretase presents several hot spots for either or

254 Ligand-dependent activation, gamma-secretase-processed cleavage, and recombining bind

255 ) complexes that characterize the sequential gamma-secretase processing of APP.

256 7I variant show no discernable impact on the gamma-secretase processing of established substrates com

257 ld type APH-1B or the APH-1B T27I variant on gamma-secretase processing of human APP, the murine Notc

258 transmembrane (TM) domains of C99 needed for gamma-secretase processing.

259 In contrast, E-Abetan stabilizers increase gamma-secretase processivity.

260 atment of AD, the precise mechanism by which gamma-secretase produces Abeta has remained elusive.

261 loid-beta (Abeta) precursor protein (APP) by gamma-secretase produces multiple species of Abeta: Abet

262 sed design of novel allosteric modulators of gamma-secretase protease activity.

263 The gamma-secretase protease and associated regulated intram

264 egulation that links the presenilins and the gamma-secretase protease to pro-inflammatory cytokine si

265 Presenilin1/gamma-secretase protects neurons from glucose deprivatio

266 substrate cleavage and its inhibition within gamma-secretase proteolipobeads were observed.

267 d protein activated by the membrane-inserted gamma-secretase proteolytic complex.

268 , which code for a minor alpha-secretase and gamma-secretase, respectively, were selectively enriched

269 sis via the activity of beta-secretase 1 and gamma-secretase, resulting in the generation of a solubl

270 The structure of gamma-secretase revealed by cryo-EM approaches suggested

271 -EM structures of TRPV1, beta-galactosidase, gamma-secretase, ribosome-EF-Tu complex, 20S proteasome

272 The mechanism by which gamma-secretase selectively recognizes and recruits ecto

273 recursor protein-cleaving enzyme 1 (BACE-1), gamma-secretase, soluble Abeta42, soluble amyloid precur

274 work offers insight into how GSAP regulates gamma-secretase specificity.

275 However, precise mechanistic information of gamma-secretase still remains unclear.

276 ese observations demonstrate that TNFR1 is a gamma-secretase substrate and suggest that gamma-secreta

277 gamma-Secretase substrate cleavage and its inhibition wi

278 Instead, gamma-secretase-substrate binding is driven by an appare

279 the theoretical basis for the development of gamma-secretase/substrate stabilizing compounds for the

280 An increasing number of gamma-secretase substrates have a role in cytokine signa

281 the importance of other APP metabolites and gamma-secretase substrates in the etiology of the diseas

282 new as well as all nine previously published gamma-secretase substrates.

283 on of six different combinations of the four gamma-secretase subunits including EGFP-tagged nicastrin

284 Here, we combined fluorescent tagging of gamma-secretase subunits with super-resolution microscop

285 under conditions of reduced glucose, the PS1/gamma-secretase system decreases neuronal losses by supp

286 under GD conditions, which suggests the PS1/gamma-secretase system protects neurons from GD-induced

287 Despite considerable interest in developing gamma-secretase targeting therapeutics for the treatment

288 of the previously proposed "dysfunction" of gamma-secretase that characterizes FAD-associated PSEN.

289 t improve the activity of one such protease, gamma secretase, through an allosteric binding site to p

290 terminal fragment is subsequently cleaved by gamma-secretase to generate a cytosolic TNFR1 intracellu

291 minal fragment (C99) that is then cleaved by gamma-secretase to generate the beta-amyloid (Abeta) fou

292 ed a unique motif in PSEN2 that directs this gamma-secretase to late endosomes/lysosomes via a phosph

293 Nonetheless, in living cells PSEN1/gamma-secretase transiently visits ADAM10 hotspots.

294 the adam13 cytoplasmic domain is cleaved by gamma secretase, translocates into the nucleus and regul

295 protein (APP) C-terminal fragments (CTFs) by gamma-secretase underlies the pathogenesis of Alzheimer'

296 y revealing the affinity of NMK-T-057 toward gamma-secretase was further validated by a fluorescence-

297 he membrane-associated SIRPalpha fragment by gamma-secretase was identified.

298 in interacts with the nicastrin component of gamma-secretase, we find that substrate ectodomain is en

299 rovided the first molecular brain imaging of gamma-secretase, which may not only accelerate our drug

300 rise to homogeneous distributions of active gamma-secretase within supported biomembranes with nativ