ライフサイエンスコーパス: secretase

1 nge contributing to the specificity of gamma-secretase.

2 the substrate's ectodomain by alpha- or beta-secretase.

3 tion to its better understood role as an APP secretase.

4 otein (APP) via cleavages by beta- and gamma-secretase.

5 tial proteolytic cleavage by BACE1 and gamma-secretase.

6 15), and its mRNA are regulated by PS1/gamma-secretase.

7 resulting from proteolytic processing by eta-secretase.

8 ein (APP) by beta-secretase (BACE) and gamma-secretase.

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

10 re it is normally processed rapidly by gamma-secretase.

11 and the downstream S3 cleavage enzyme, gamma-secretase.

12 olecular imaging tools for visualizing gamma-secretase.

13 leading to loss-of-function of ADAM17 alpha-secretase.

14 uggesting a functional conservation of gamma-secretase.

15 ain requires the enzymatic activity of gamma-secretase.

16 uired for stoichiometric inhibition of gamma-secretase.

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

18 se complex containing active beta- and gamma-secretases.

19 d precursor protein (APP) by beta- and gamma-secretases.

20 recursor protein (APP) by the beta and gamma secretases.

21 Egr-1 silencing also reduces levels of beta-secretase 1 (BACE-1) and BACE-1-cleaved amyloid precurso

22 etastasis; MMP-9, in neuropathic pain), beta-secretase 1 (BACE-1, an aspartic protease in Alzheimer's

23 beta-secretase 1 (BACE1) is a key enzyme in the generation of

24 tment and siRNA knockdown revealed that beta-secretase 1 (BACE1) is the protease responsible for Nogo

25 Through intravenous delivery of NLC-beta-secretase 1 (BACE1) siRNA complexes we show effective BA

26 Previous in vitro studies showed that beta-secretase 1 (BACE1), the key-enzyme of amyloidogenesis,

27 embrane proteolysis via the activity of beta-secretase 1 and gamma-secretase, resulting in the genera

28 quential proteolytic cleavage of APP by beta secretase 1 enzyme (BACE1) and gamma-secretase leads to

29 Delta-secretase, a lysosomal asparagine endopeptidase (AEP), s

30 1 and 2) are the catalytic subunits of gamma-secretase, a multiprotein protease that cleaves amyloid

31 PS1/gamma-secretase activates the transcription factor, cAMP respo

32 The mechanism by which gamma-secretase activating protein (GSAP) regulates gamma-secr

33 ocalization significantly influence its beta secretase activity and amyloid-beta (Abeta) production.

34 hermore, membralin deficiency enhances gamma-secretase activity and neuronal degeneration.

35 urthermore, knockout of IFITM3 reduces gamma-secretase activity and the formation of amyloid plaques

36 ther validated by a fluorescence-based gamma-secretase activity assay, which confirmed inhibition of

37 or X (Inh X), a compound that inhibits gamma-secretase activity before exposing to MAG or CNS myelin

38 SAP in cultured cells directly reduces gamma-secretase activity for Abeta production, but not for Not

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

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

41 a strong and positive correlation with gamma-secretase activity in samples from patients with late-on

42 reports, we and others have shown that gamma-secretase activity is enriched in mitochondria-associate

43 tal players, in addition to escalating delta-secretase activity to cleave alpha-Syn and promotes its

44 ) mutations lead to either (2) reduced gamma-secretase activity, (3) altered protein stability or (4)

45 ation of PS1 at Ser367 does not affect gamma-secretase activity, but has a dramatic effect on Abeta l

46 cause loss of Presenilin function and gamma-secretase activity, including impaired Abeta production

47 survive into adulthood despite loss of gamma-secretase activity.

48 ract with BACE1 by negatively modulating its secretase activity.

49 levels through indirect inhibition of gamma-secretase activity.

50 side of TMD4 affect Abeta42-generating gamma-secretase activity.

51 lzheimer's disease that exhibit higher gamma-secretase activity.

52 en delivered to the ER for cleavage by gamma-secretase, acts as a lipid-sensing peptide that forms re

53 expression of AD-relevant genes: BDNF, alpha-secretase (ADAM10), MINT2, FE65, REST, SIRT1, BIN1, and

54 orders associated with augmentation of delta-secretase, alpha-Syn, and MAOB.

55 Inhibition of gamma-secretase also decreases neuronal survival under GD cond

56 delta-secretase, also known as asparagine endopeptidase (AEP)

57 vel APP secretases (including delta- and eta-secretases, alternative beta-secretases) and additional

58 in 1 (PS1) is the catalytic subunit of gamma-secretase, an enzyme complex responsible for the maturat

59 SRPK2 phosphorylates serine 226 on delta-secretase and accelerates its autocatalytic cleavage, le

60 rotein kinase 2 (SRPK2) phosphorylates delta-secretase and enhances its enzymatic activity.

61 It reduces both the beta-secretase and gamma-secretase cleavages of the amyloid p

62 and Psen1 mRNA, which code for a minor alpha-secretase and gamma-secretase, respectively, were select

63 Inhibition of gamma-secretase and metalloproteinase proteolysis in the NOTCH

64 compounds for their potential to bind gamma-secretase and observed that 3-(3'4',5'-trimethoxyphenyl)

65 neurons and astrocytes, which binds to gamma-secretase and upregulates its activity, thereby increasi

66 ) complex (~5 MD) containing beta- and gamma-secretases and holo-APP was catalytically active in vitr

67 delta- and eta-secretases, alternative beta-secretases) and additional metabolites, some of which ma

68 ar calcium, (2) activation of the BACE1 beta-secretase, and (3) ErbB4 receptor activation.

69 entially cleaved by alpha-, beta-, and gamma-secretase, and the released CX3CL1 intracellular domain

70 ment that reverses axon defects in PS1/gamma-secretase- and EphA3-deficient hippocampal neurons.

71 gamma-Secretases are a family of intramembrane-cleaving protea

72 We visualized gamma-secretase association with substrates like amyloid precu

73 1-oriented stub is further cleaved by gamma-secretase at an -like site five amino acids N-terminal t

74 rt that APP is processed by endogenous alpha-secretase at the trans-Golgi network (TGN) of both trans

75 olved in the generation of Abeta is the beta-secretase BACE, for which powerful inhibitors have been

76 96) phosphorylation, and decreases both beta-secretase (BACE) and APOEepsilon4 gene expression.

77 the amyloid precursor protein (APP) by beta-secretase (BACE) and gamma-secretase.

78 ine templates for use in SAR studies of beta-secretase (BACE) inhibitors and also as versatile ligand

79 escued by pharmacological modulation of beta-secretase (BACE).

80 e of amyloid precursor protein (APP) by beta-secretase BACE1 initiates the production and accumulatio

81 Inhibition of beta-secretase BACE1 is considered one of the most promising

82 amyloid precursor protein (APP) by the beta-secretase BACE1 is the initial step of the amyloidogenic

83 A growing subset of beta-secretase (BACE1) inhibitors for the treatment of Alzhei

84 The beta-secretase (BACE1) initiates processing of the amyloid pr

85 tant step in its subsequent cleavage by beta-secretase (BACE1).

86 The beta-secretase, BACE1 is a protease needed to generate active

87 along the amyloidogenic pathway by the beta-secretase, BACE1, generating beta-amyloid (Abeta), or al

88 ) is a major physiological substrate of beta-secretase (beta-site amyloid precursor protein-cleaving

89 compound 11, that specifically blocks delta-secretase but not other related cysteine proteases.

90 est that the enzymatic function of PS1/gamma-secretase can be modulated by its 'phosphorylated' and '

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

92 Herein, we demonstrate that gamma-secretase catalysis is driven by the stabilization of an

93 C-terminal fragments of APP from both alpha-secretase cleavage (alpha-CTF, named C83 according to it

94 ess the frequency of susceptibility to gamma-secretase cleavage among human RTKs.

95 Both mutants impaired gamma-secretase cleavage and also altered its cleavage specifi

96 er protein that undergoes very similar gamma-secretase cleavage is the p75 neurotrophin receptor.

97 tome of ISVAID suggests that beta- and alpha-secretase cleavage of APP cuts inside the interaction do

98 These compounds affected beta-secretase cleavage of APP similarly to 1a.

99 mutants decrease the EphB4-stimulated gamma-secretase cleavage of ephrinB2 and reduce production of

100 rs and catalyzes the non-amyloidogenic alpha-secretase cleavage of the Alzheimer's precursor protein

101 ation of the mutant APP, and inhibited gamma-secretase cleavage of the mutant C99 to generate Abeta,

102 ation of the mutant APP, and inhibited gamma-secretase cleavage of the mutant C99 to generate amyloid

103 eta production, which are abrogated by delta-secretase cleavage of TrkB in AD.

104 and increased secretion of the soluble alpha-secretase cleavage product sAPPalpha.

105 A detrimental APP mutation at the beta-secretase cleavage site linked to early-onset AD found i

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

107 ecause this residue is just before the gamma-secretase cleavage site, we then investigated whether th

108 ISVAID contains the beta- and alpha-secretase cleavage sites of APP: proteomic analysis of t

109 ydrogen bonds are at or near preferred gamma-secretase cleavage sites, suggesting that the sequence o

110 ecipient cells, and upon activation by gamma-secretase cleavage, induces NOTCH-specific gene expressi

111 ty of this hinge might be critical for gamma-secretase cleavage, we mutated one of the glycine residu

112 family members AXL or TYRO3 depends on gamma-secretase cleavage.

113 It reduces both the beta-secretase and gamma-secretase cleavages of the amyloid precursor protein (AP

114 sides the canonical alpha-, beta-, and gamma-secretases, cleave the amyloid precursor protein (APP) a

115 Hence, delta-secretase cleaves TrkB and blunts its phosphorylation of

116 Delta-secretase cleaves TrkB at N365 and N486/489 residues and

117 form and impairs the integrity of the gamma-secretase complex as well as its catalytic activity towa

118 at presenilins (PS), components of the gamma-secretase complex frequently mutated in familial Alzheim

119 The amount of IFITM3 in the gamma-secretase complex has a strong and positive correlation

120 eptide ratio generated by the HMW beta/gamma-secretase complex indistinguishably from that observed i

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

122 smembrane substrates by the presenilin-gamma-secretase complex is preceded and regulated by shedding

123 The gamma-secretase complex is responsible for the cleavage of sev

124 Notch1 and Rheb esRNA and component of gamma-secretase complex presenilin 1 from Tsc1-null cells to w

125 from the Abeta precursor protein, the gamma-secretase complex produces the Abeta peptides associated

126 their ligands (Jagged 1-2, DLL1,3,4), gamma-secretase complex proteins (Presenilin 1, Nicastrin), an

127 protein products partially compose the gamma-secretase complex that cleaves Abeta from amyloid precur

128 brane peptidomimetic inhibitors of the gamma-secretase complex that contain an N-terminal helical pep

129 ein nicastrin (NCSTN), a member of the gamma-secretase complex that functions to recruit substrates f

130 is generated from holo-APP by a BACE1-gamma-secretase complex that provides sequential, efficient RI

131 tify nicastrin, a key component of the gamma-secretase complex, as a membralin binding protein and me

132 1 (PS1), the catalytic subunit of the gamma-secretase complex, cleaves betaCTF to produce Abeta.

133 y the Presenilin 1 (PS1) enzyme in the gamma-secretase complex, generating Abeta.

134 ould allow visualization of the active gamma-secretase complex, poised for intramembrane proteolysis,

135 n role as the catalytic subunit of the gamma-secretase complex, selective phosphorylation of PS1 on S

136 n role as the catalytic subunit of the gamma-secretase complex, selective phosphorylation of PS1 on S

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

138 APP-cleaving enzyme 1 (BACE1) and the gamma-secretase complex.

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

140 gamma-Secretase complexes (GSECs) are multimeric membrane prot

141 gamma-Secretase complexes achieve the production of amyloid pe

142 We show that PS1-containing gamma-secretase complexes were targeted to the plasma membrane

143 llumination microscopy revealed single gamma-secretase complexes with a monodisperse distribution and

144 nd metalloprotease 10 (ADAM10) and the gamma-secretase component presenilin-1.

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

146 Recent determination of intact human gamma-secretase cryo-electron microscopy structure has opened

147 Similarly, chemical inhibition of beta-secretase decreased mitochondrial respiration, suggestin

148 PS1/gamma-secretase-deficient neurons show decreased phosphorylate

149 To escape this restriction, Gag promotes secretase-dependent cleavage of APP, resulting in the ov

150 The DSCAM ICD is released by gamma-secretase-dependent cleavage, and both the DSCAM and DSC

151 In conclusion, PS/gamma-secretase-dependent EphA3 cleavage mediates axon growth

152 ess GH activates Notch1 signaling in a gamma-secretase-dependent manner.

153 migration and induces their death via gamma-secretase-dependent regulated intramembrane proteolysis

154 Thus, localization of gamma-secretases determines substrate specificity, while FAD-c

155 resolution microscopy for the study of gamma-secretase distribution and dynamics in the membrane.

156 of soluble BCMA (sBCMA); inhibition of gamma-secretase enhanced surface expression of BCMA and reduce

157 s shared certain brain areas with high gamma-secretase expression, suggesting a functional conservati

158 tivity in vitro SPP is a member of the gamma-secretase family, and mice lacking SPP are embryonic let

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

160 enzyme 1 (BACE1) is the major neuronal beta-secretase for Abeta generation.

161 enzyme 1 (BACE1) is the major neuronal beta-secretase for amyloid-beta generation and is degraded in

162 ally, AIBP triggered relocalization of gamma-secretase from lipid rafts to nonlipid rafts where it cl

163 Impaired gamma-secretase function is associated with the development of

164 Consistent with loss of gamma-secretase function, Psen1(LF/LF) rats exhibited low leve

165 r protein (APP), first by the action of beta-secretase, generating the beta-C-terminal fragment (beta

166 surface by the ubiquitous multisubunit gamma-secretase (GS) complex, which reduces ligand density on

167 Structurally, beta-secretase has a very large binding site (1000 angstrom)

168 h TrkB and APP are robustly cleaved by delta-secretase in AD brains, accompanied by mitigated TrkB si

169 noprecipitated and cofractionated with gamma-secretase in cultured cells and in mouse and human brain

170 esting a novel direct role for PS1 and gamma-secretase in mitochondrial stress.

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

172 with the discovery of a number of novel APP secretases (including delta- and eta-secretases, alterna

173 id precursor protein (APP) cleavage by gamma-secretase, increasing the proportion of longer amyloidog

174 and reduced Notch signaling, either by gamma-secretase inhibition or loss of Dll4, rescue retinal ang

175 logic blockage of Notch activation via gamma-secretase inhibition.

176 revented by combined chemical beta and gamma-secretase inhibition.

177 ADAM10 inhibitor (GI254023X) and gamma-secretase inhibitor (DAPT) were used to inhibit CD44 cle

178 ed the combination between miR-34a and gamma-secretase inhibitor (gammaSI), Sirtinol or zoledronic ac

179 stant CCA cell lines pretreated with a gamma-secretase inhibitor (GSi) cocktail demonstrated the anti

180 ess to 6-CF(3)-substituted 1,3-thiazine beta-secretase inhibitor 2.

181 Th2 switch was IL4 independent, but a gamma-secretase inhibitor abrogated it, and it was not found i

182 harmacological inhibition of Notch1 by gamma-secretase inhibitor DAPT (N-[N-(3,5-Difluorophenacetyl)-

183 ing Notch receptor activation with the gamma-secretase inhibitor DAPT (N-[N-(3,5-difluorophenacetyl)-

184 and chronic Notch blockade through the gamma-secretase inhibitor dibenzazepine down-regulated LRP5/6

185 sues from mice given injections of the gamma-secretase inhibitor dibenzazepine, and mice with intesti

186 d with intrahippocampal injection of a gamma-secretase inhibitor evaluates the impact of Abeta fluctu

187 n orally bioactive and brain permeable delta-secretase inhibitor in mouse models of AD.

188 ption of HUVEC-based tube formation by gamma-secretase inhibitor L1790 confirmed the critical role of

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

190 , these findings demonstrate that this delta-secretase inhibitor may be an effective clinical therape

191 e response rate after therapy with the gamma-secretase inhibitor PF-03084014 in patients with recurre

192 tical neurons, and can be prevented by gamma-secretase inhibitor treatment.

193 ynergistic effect, when combined with a beta-secretase inhibitor, BACE IV.

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

195 d identified a non-toxic and selective delta-secretase inhibitor, termed compound 11, that specifical

196 -phenylglucine t-butyl ester (DAPT), a gamma-secretase inhibitor, which inhibits Notch signaling.

197 es of blocking Abeta production with a gamma-secretase inhibitor.

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

199 Gamma-secretase inhibitors (GSI) and anti-Notch4 were all capa

200 er, inhibition of NOTCH signaling with gamma-secretase inhibitors (GSIs) has shown limited antileukem

201 d receptors, as well as small-molecule gamma-secretase inhibitors (GSIs), have been developed to inte

202 e have recently reported that clinical gamma-secretase inhibitors (GSIs), initially developed to mana

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

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

205 gamma-secretase inhibitors are commonly used to probe NOTCH fu

206 highlight the potential application of gamma-secretase inhibitors as a therapeutic target in people w

207 MPTP opening was directly regulated by gamma-secretase inhibitors independent on organelle calcium mo

208 el therapies, including nelarabine and gamma-secretase inhibitors, in adult patients with T-cell ALL.

209 bsence or reduction of PS1, as well as gamma-secretase inhibitors, increases neuronal miR-212, which

210 hods, the most common of which are the gamma-secretase inhibitors, which produce a pan-Notch inhibiti

211 a surrogate for the design of renin and beta-secretase inhibitors.

212 ck-density areas that are sensitive to gamma-secretase inhibitors.

213 Cleavage of APP by BACE1/beta-secretase initiates the amyloidogenic cascade leading to

214 alpha-Secretase initiates the non-amyloidogenic pathway preven

215 We asked whether beta- and gamma-secretases interact to mediate efficient sequential proc

216 residue CTF (C99)]- and Notch-specific gamma-secretase interaction assays identified a unique ErbB2-c

217 gamma-secretase is a macromolecular complex that catalyzes int

218 gamma-Secretase is a membrane-embedded aspartyl protease compl

219 gamma-Secretase is a multi-subunit enzyme whose aberrant activ

220 gamma-Secretase is a prime drug target for AD; however, its br

221 ils implicated in Alzheimer's disease, gamma-secretase is an important target for developing therapeu

222 gamma-secretase is an intramembrane protease complex that cata

223 gamma-Secretase is an intramembranous protein complex composed

224 gamma-secretase is composed of four subunits: nicastrin (NCT)

225 Delta-secretase is highly phosphorylated in human AD brains, t

226 oid precursor protein C99 substrate by gamma-secretase is implicated in Alzheimer's disease pathogene

227 e findings reveal a mechanism in which gamma-secretase is modulated by neuroinflammation via IFITM3 a

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

229 gamma-secretase is responsible for the proteolysis of amyloid

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

231 d subsequent intramembrane cleavage by gamma-secretase leads to release of a soluble intracellular re

232 by beta secretase 1 enzyme (BACE1) and gamma-secretase leads to the production and release of Abeta40

233 ng amyloid precursor protein (APP) and gamma-secretase levels in lipid rafts.

234 its structure is atomically resolved, gamma-secretase localization in the membrane in situ relies mo

235 phenotype than either global Notch or gamma-secretase loss.

236 Here, we undertook to determine whether the secretase machinery is actively processing APP in EVs is

237 n living cells, sptPALM revealed PSEN1/gamma-secretase mainly with directed motility and frequenting

238 hat cleavage of APP by either beta- or alpha-secretase may inactivate the ISVAID, thereby enhancing g

239 hagy-mediated cell death by inhibiting gamma-secretase-mediated activation of Notch signaling.

240 brane is considered the major site for alpha-secretase-mediated APP cleavage, but other cellular loca

241 Upon beta-secretase-mediated cleavage of the beta C-terminal fragm

242 ken together, these data indicate that gamma-secretase-mediated cleavage provides an additional signa

243 ng meprin beta-mediated and decreasing alpha-secretase-mediated processing of APP at the plasma membr

244 PS1/gamma-secretase mediates axon growth by inhibiting RhoA signal

245 Hence, pharmacological inhibition of gamma-secretase might lead to the subsequent inhibition of Not

246 of observed NOTCH receptor engagement, gamma-secretase modulation was rationalized as a therapeutic o

247 tarting from RO6800020 (1), our former gamma-secretase modulator (GSM) lead compound, we utilized seq

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

249 We used our recently developed gamma-secretase modulators (GSMs) and synthesized our GSM-base

250 lose three structurally differentiated gamma-secretase modulators (GSMs) based on an oxadiazine scaff

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

252 of a novel series of oxadiazine-based gamma secretase modulators obtained via isosteric amide replac

253 gamma-Secretase modulators, a class of Alzheimer's disease the

254 isolated complex responded properly to gamma-secretase modulators.

255 transmembrane protein 3 (IFITM3) as a gamma-secretase modulatory protein, and establish a mechanism

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

257 ontains the sites cleaved by beta- and alpha-secretases: our data suggest that beta-/alpha cleavage o

258 Our findings support that delta-secretase phosphorylation by SRPK2 plays a critical role

259 cies, including breast, and the enzyme gamma-secretase plays an important role in the activation and

260 along the nonamyloidogenic pathway by alpha-secretase, precluding Abeta production.

261 site, providing the mechanism by which gamma-secretase preferentially cleaves APP in three amino acid

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

263 Druggability simulations show that gamma-secretase presents several hot spots for either orthoste

264 s identify the TGN as a major site for alpha-secretase processing in HeLa cells and primary neurons a

265 gher than that of C99, indicating that alpha-secretase processing is the major pathway and that BACE1

266 lexes that characterize the sequential gamma-secretase processing of APP.

267 iant show no discernable impact on the gamma-secretase processing of established substrates compared

268 e APH-1B or the APH-1B T27I variant on gamma-secretase processing of human APP, the murine Notch deri

269 embrane (TM) domains of C99 needed for gamma-secretase processing.

270 endogenous APP in the TGN and enhanced alpha-secretase processing.

271 ignificance of the ISVAID and of beta-/alpha-secretase-processing of APP using various ISVAID-derived

272 ides representing the product of beta-/alpha-secretase-processing of ISVAID did not alter excitatory

273 ontrast, E-Abetan stabilizers increase gamma-secretase processivity.

274 eta (Abeta) precursor protein (APP) by gamma-secretase produces multiple species of Abeta: Abeta40, s

275 sign of novel allosteric modulators of gamma-secretase protease activity.

276 Presenilin1/gamma-secretase protects neurons from glucose deprivation-indu

277 ate cleavage and its inhibition within gamma-secretase proteolipobeads were observed.

278 h code for a minor alpha-secretase and gamma-secretase, respectively, were selectively enriched in wi

279 a the activity of beta-secretase 1 and gamma-secretase, resulting in the generation of a soluble intr

280 ructures of TRPV1, beta-galactosidase, gamma-secretase, ribosome-EF-Tu complex, 20S proteasome and RN

281 nce, our study supports that C/EBPbeta/delta-secretase signaling mediates PD pathogenesis via regulat

282 or protein-cleaving enzyme 1 (BACE-1), gamma-secretase, soluble Abeta42, soluble amyloid precursor pr

283 offers insight into how GSAP regulates gamma-secretase specificity.

284 gamma-Secretase substrate cleavage and its inhibition within g

285 Instead, gamma-secretase-substrate binding is driven by an apparent tig

286 eoretical basis for the development of gamma-secretase/substrate stabilizing compounds for the preven

287 well as all nine previously published gamma-secretase substrates.

288 re, we combined fluorescent tagging of gamma-secretase subunits with super-resolution microscopy in f

289 conditions of reduced glucose, the PS1/gamma-secretase system decreases neuronal losses by suppressin

290 GD conditions, which suggests the PS1/gamma-secretase system protects neurons from GD-induced death.

291 del of AD pathology, phosphorylation of beta-secretase, the enzyme involved in the formation of amylo

292 in a preventive mode, i.e., gamma- and beta-secretase; the rationale behind these two targets; and t

293 d precursor protein (APP) is cleaved by beta-secretase to generate a 99-aa C-terminal fragment (C99)

294 fragment (C99) that is then cleaved by gamma-secretase to generate the beta-amyloid (Abeta) found in

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

296 dam13 cytoplasmic domain is cleaved by gamma secretase, translocates into the nucleus and regulates m

297 n (APP) C-terminal fragments (CTFs) by gamma-secretase underlies the pathogenesis of Alzheimer's dise

298 aling the affinity of NMK-T-057 toward gamma-secretase was further validated by a fluorescence-based

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

300 as an important crossroad for APP and these secretases, with major implications for APP processing a