ライフサイエンスコーパス: BACE

1 BACE activity correlated with formic acid-extractable A

2 BACE cleavage of the APP leads to formation of the Abeta

3 BACE inhibition led to a significant time- and dose-depe

4 BACE inhibition resulted in decreased labeled sAPPbeta a

5 BACE initiates the production of beta-amyloid (Abeta), t

6 BACE is a transmembrane protease with beta-secretase act

7 BACE is an aspartyl protease, and there is significant e

8 BACE is targeted through the secretory pathway to the pl

9 BACE levels are elevated in AD brain, and increasing evi

10 BACE, a beta-secretase, is an attractive potential disea

11 BACE-1 (beta-site amyloid precursor protein cleaving enz

12 BACE-1 cleavage of APP is the committed step in Abeta sy

13 BACE-1 has been shown to be the major beta-secretase and

14 BACE-1 inhibition has the potential to provide a disease

15 BACE-1 inhibitory potency was increased (0.9 microM to 1

16 BACE-1 is the beta-secretase responsible for the initial

17 BACE-1 levels also were a mean of 7-fold higher in ADEs

18 ession of APP or beta-APP-cleaving enzyme 1 (BACE-1) using short hairpin RNA constructs.

19 amyloid precursor protein-cleaving enzyme 1 (BACE-1), gamma-secretase, soluble Abeta42, soluble amylo

20 e of APP by beta-site APP cleaving enzyme 1 (BACE-1), is the primary cause of the endosome enlargemen

21 amyloid-precursor-protein-cleaving enzyme 1 (BACE-1), with many big pharma companies expending great

22 beta-Site APP cleaving enzyme-1 (BACE-1) is the predominant enzyme involved in beta-secre

23 ing also reduces levels of beta-secretase 1 (BACE-1) and BACE-1-cleaved amyloid precursor protein (AP

24 precursor protein (APP) by beta-secretase 1 (BACE-1) followed by gamma-secretase.

25 or its radical capture and beta-secretase 1 (BACE-1) inhibitory activities.

26 beta-Secretase 1 (BACE-1) is an attractive therapeutic target for the trea

27 Memapsin 2 (BACE, beta-secretase) is a membrane-associated aspartic

28 ceived a low, medium, or high dose of MBI-5 (BACE inhibitor) or vehicle in a four-way crossover desig

29 Conversely, a BACE inhibitor decreased sAPPbeta and Abeta peptides wit

30 escribes the discovery and optimization of a BACE-1 inhibitor series containing an unusual acyl guani

31 ry 10 years ago, much has been learned about BACE.

32 1 binds to the BACE-1 promoter and activates BACE-1 transcription.

33 f Egr-1 induces BACE-1 expression, activates BACE-1, promotes amyloidogenic APP processing, and enhan

34 ays, the properties of a potent, cell-active BACE-1 inhibitor are described.

35 We evaluated BACE activity, BACE protein, and formic acid-extractable A beta levels

36 not different between 3xTg-AD versus 3xTg-AD/BACE(-/-) mice, thereby demonstrating that tau pathology

37 P immunostaining was detected in the 3xTg-AD/BACE(-/-) mice.

38 activity has obvious therapeutic advantages, BACE-1 also cleaves numerous other substrates with impor

39 and APP and might therefore directly affect BACE-APP complex formation.

40 After BACE cleavage, APP becomes a substrate for gamma-secreta

41 However, although BACE inhibition can reduce cerebral Abeta levels, whethe

42 9 represents a unique molecular shape among BACE inhibitors reported to potently lower central Abeta

43 glycosaminoglycan-binding proteins FGF-1 and BACE, and for the heterotypic adhesion molecules JAM-B a

44 uces levels of beta-secretase 1 (BACE-1) and BACE-1-cleaved amyloid precursor protein (APP) metabolit

45 study, we found that the levels of Abeta and BACE-1 are significantly reduced in the brains of mice l

46 APP and BACE are co-internalized from the cell surface to early

47 e much research, neuronal locales of APP and BACE-1 convergence and APP cleavage remain unclear.

48 n hippocampal neurons, we found that APP and BACE-1 interacted in both biosynthetic and endocytic com

49 In axons, APP and BACE-1 were cotransported, and they also interacted duri

50 ylcholinesterase, butyrylcholinesterase, and BACE-1, dual Abeta42 and tau antiaggregating activity, a

51 nces tau phosphorylation, activates Cdk5 and BACE-1, and accelerates amyloidogenic APP processing.

52 pectively controlling activities of Cdk5 and BACE-1, suggesting that Egr-1 is a potential therapeutic

53 yl proteases such as cathepsin D (Cat D) and BACE-2.

54 ity used to identify inhibitors of furin and BACE.

55 nt with anti-Abeta antibody gantenerumab and BACE inhibitor RO5508887, either as mono- or combination

56 ctivity using a beta-secretase inhibitor and BACE knock-out cells, indicating that meprin beta acts i

57 establish a linkage between Abeta levels and BACE, we examined BACE protein, mRNA expression and enzy

58 onstrate correlation between Abeta loads and BACE elevation and also suggest that as a consequence, B

59 Moreover, sorLA and BACE also coimmunoprecipitate.

60 The convergence of APP (substrate) and BACE-1 (enzyme) is a rate-limiting, obligatory event tri

61 These data indicate an absence of TACE and BACE competition for the APP substrate.

62 tion using a highly specific BACE1 antibody, BACE-Cat1, made in BACE1-/- mice, which mount a robust a

63 e molecular dynamics simulations on both apo BACE-1 and five BACE-1-inhibitor complexes to examine th

64 ntrols the conformational flexibility of apo BACE-1, whereas bound inhibitors largely limit the motio

65 'Icelandic' mutation greatly attenuates APP-BACE-1 interactions, suggesting a mechanistic basis for

66 plementation, for visualizing in cellulo APP-BACE-1 interactions as a simple on/off signal.

67 However, as both APP/BACE-1 are highly expressed in brain, mechanisms preclud

68 sis via the secretory pathway, dendritic APP/BACE-1-containing vesicles are largely segregated in phy

69 afficking strategies that normally limit APP/BACE-1 proximity and also uncover a pathway routing APP

70 Exploring dynamic localization of APP/BACE-1 in cultured hippocampal neurons, we found that af

71 A partitioning/convergence of APP/BACE-1 vesicles is also apparent in control/AD brains, r

72 ances Abeta production by increasing the APP/BACE-1 convergence in endolysosomal compartments.

73 them resistant to BACE cleavage, as well as BACE inhibition, result in the loss of axonal puncta and

74 and an intrinsic inverse correlation between BACE expression and oxidative metabolism at the first sy

75 strong negative correlation existed between BACE labeling intensity and CO or SDH activity among ind

76 st that there is a close interaction between BACE and LRP on the cell surface, and that LRP is a nove

77 Blocking BACE-1 action, on the other hand, blocks Egr-1-induced a

78 We found that both BACE mRNA and protein expression is elevated in vivo in

79 In normal bulb, BACE was expressed predominantly in the glomerular layer

80 tibodies produce nonspecific background, but BACE-Cat1 immunolabels BACE1 only.

81 eavage of amyloid precursor protein (APP) by BACE-1 (beta-site APP cleaving enzyme-1) is the rate-lim

82 stand the effect of sorLA on APP cleavage by BACE, we analyzed whether sorLA interacts with APP and/o

83 or the C-terminal APP fragment generated by BACE-1 (betaCTF), all of which elevate the levels of bet

84 RG1 and NRG3 are constitutively processed by BACE and accumulate on axons where they interact with Er

85 2' positions This substrate was processed by BACE-1 approximately 10 times more efficiently than was

86 nders APP less susceptible to proteolysis by BACE without inhibiting BACE enzymatic activity or the p

87 ity and/or oxidative metabolism, we compared BACE expression with cytochrome c oxidase (CO) or succin

88 tion and also suggest that as a consequence, BACE elevation may lead to increased Abeta production an

89 Considering BACE-1 is optimally active in an acidic environment, our

90 ation and in cells exposed to a conventional BACE inhibitor.

91 e movements compared to previously described BACE structures.

92 review summarizes BACE properties, describes BACE translation dysregulation in AD, and discusses BACE

93 o suggests new possibilities for discovering BACE-1-targeted compounds with more complex mechanisms o

94 anslation dysregulation in AD, and discusses BACE physiological functions in sodium current, synaptic

95 ly potent, selective and in vivo efficacious BACE inhibitors.

96 Enhanced BACE labeling was confirmed by measurements of elevated

97 homology to the mammalian processing enzyme BACE, recognizes the PEXEL motif and cleaves it at the c

98 ite Abeta precursor protein cleaving enzyme (BACE) 1 and BACE2.

99 e amyloid precursor protein-cleaving enzyme (BACE) and Abeta in naive mice, using Western blot, immun

100 PP) and human beta-site APP-cleaving enzyme (BACE) and found that they develop neuronal loss and huma

101 ntially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides

102 eta precursor protein (APP)-cleaving enzyme (BACE) and gamma-secretase, the proteases responsible for

103 reduction of beta-site APP cleaving enzyme (BACE) in these ArcTau mice decreases soluble Abeta oligo

104 Beta-site APP-cleaving enzyme (BACE) is required for production of the Alzheimer's dise

105 Beta-APP cleaving enzyme (BACE) is responsible for the first of two proteolytic cl

106 eta peptides, beta-site APP-cleaving enzyme (BACE), presenilin-1 (PS-1), caspase-3, and caspase-media

107 cleavage in a beta-site APP-cleaving enzyme (BACE)-dependent manner.

108 oid precursor protein (APP)-cleaving enzyme (BACE).

109 ase named the beta-site APP-cleaving enzyme (BACE).

110 tein (APP) by beta-site APP cleaving enzyme (BACE)1 and gamma-secretase.

111 e amyloid precursor protein cleaving enzyme (BACE-1) inhibitors containing an aminoethylene (AE) tetr

112 iating with beta-site APP-converting enzyme (BACE)1, thereby modulating APP processing.

113 ta-secretase (beta-site APP cleaving enzyme, BACE) involved in APP processing provides a pharmaceutic

114 r protein) to the beta-site-cleaving enzymes BACE and BACE2, the gamma-site-cleaving enzymes presenil

115 peptides by beta-site APP cleaving enzymes (BACE).

116 resonance energy transfer assay to evaluate BACE-APP interactions in cells.

117 We evaluated BACE activity, BACE protein, and formic acid-extractable

118 e between Abeta levels and BACE, we examined BACE protein, mRNA expression and enzymatic activity in

119 tion of endogenous and ectopically expressed BACE in a variety of cell types, including primary neuro

120 hysical and NMR-based methods as a bona fide BACE inhibitor.

121 es were synthesized with the goal of finding BACE-1 inhibitors as a treatment for Alzheimer's disease

122 mics simulations on both apo BACE-1 and five BACE-1-inhibitor complexes to examine the effect of pH o

123 n were used to identify novel inhibitors for BACE-1.

124 isothiourea hit with a K(d) of 15 microM for BACE-1.

125 adaptor protein GGA3, which is required for BACE lysosomal degradation, consequently stabilizing BAC

126 o gain insight into the key requirements for BACE-1 and GSK-3beta inhibition.

127 expending great resources in the search for BACE-1 inhibitors.

128 Furthermore BACE activity increased significantly with age in mouse,

129 c interventions target APP processing (e.g., BACE inhibitors), those strategies may alter APP/APLP ph

130 is occlusion resulted in elevated glomerular BACE labeling in the deprived bulbs relative to the nond

131 hat prevents BACE-APP interactions and hence BACE cleavage of APP.

132 site APP-cleaving enzyme 1 (BACE1, or herein BACE).

133 Human BACE, also known as beta-secretase, shows promise as a p

134 esponding histopathologies, confirming human BACE as the key parameter in amyloid pathogenesis.

135 9) shows potent combined inhibition of human BACE-1 and ChEs, as well as good antioxidant and CNS-per

136 They are also potent inhibitors of human BACE-1, better than the parent flavonoid, apigenin.

137 Potent iminohydantoin BACE-1 inhibitors have been obtained, validating the mol

138 To test whether sorLA impacts BACE-APP interactions, we used a fluorescence resonance

139 Herein, we review the major advances in BACE-1 drug discovery, from single-target small molecule

140 We show that increases in BACE and beta-secretase activity are due to posttranslat

141 vels of GGA3, an adaptor protein involved in BACE trafficking, are reduced, while BACE levels are inc

142 silencing of ShcC also led to reductions in BACE levels in H4-FL-APP cells.

143 oscopic pKa values of titratable residues in BACE-1 including its aspartyl dyad are computed and comp

144 Isoflurane may increase BACE levels by reducing BACE degradation.

145 Increased BACE levels in p25 overexpressing mice correlated with e

146 induce apoptosis, which, in turn, increases BACE and gamma-secretase levels and Abeta secretion.

147 ary neurons, overexpression of Egr-1 induces BACE-1 expression, activates BACE-1, promotes amyloidoge

148 While inhibiting BACE-1 activity has obvious therapeutic advantages, BACE

149 le to proteolysis by BACE without inhibiting BACE enzymatic activity or the processing of other BACE

150 st display library that selectively inhibits BACE-1 activity toward APP by binding the APP substrate

151 and also uncover a pathway routing APP into BACE-1-containing organelles, triggering amyloidogenesis

152 the amyloidogenic pathway-APP is routed into BACE-1-positive recycling endosomes via a clathrin-depen

153 By leveraging the knowledge of the ligand-BACE-1 recognition features generated from the isocytosi

154 reatment with drugs that indirectly modulate BACE processing of APP but spare other BACE substrates a

155 Brain penetrant small molecule BACE inhibitors with high ligand efficiencies have been

156 micromolar hit into a single-digit nanomolar BACE-1 inhibitor in both radioligand binding and cell-ba

157 d series and its optimization into nanomolar BACE-1 inhibitors are the subject of the companion paper

158 ligands represent a new type of nonpeptidic BACE-1 inhibitor motif that has not been described in th

159 t of AD and could be safer than nonselective BACE inhibitor drugs.

160 Notably, BACE reduction decreases the postsynaptic mislocalizatio

161 as resulted in the identification of a novel BACE binder featuring spiropyrrolidine framework.

162 on the cell surface, and that LRP is a novel BACE substrate.

163 ts in the redistribution and accumulation of BACE in the late endosomal/lysosomal compartments (lysos

164 ray with the two catalytic aspartic acids of BACE-1 (Asp(32), Asp(228)).

165 ggest that Egr-1 plays role in activation of BACE-1 and acceleration of Abeta synthesis in AD brain.

166 synthesis via transcriptional activation of BACE-1 and suggest that Egr-1 plays role in activation o

167 ese data highlight the potential benefits of BACE inhibition for the effective treatment of a wide ra

168 Moreover, we found few changes of BACE protein and mRNA levels in Swedish mutated amyloid

169 two novel assays for the characterization of BACE-1 inhibitors are reported.

170 tial to a full in silico characterization of BACE-1.

171 H-imidazoles are described as a new class of BACE-1 inhibitors for the treatment of Alzheimer's disea

172 e describe the discovery of a novel class of BACE-1 inhibitors represented by sulfamide 14g, using a

173 highlight the potential of this new class of BACE-1 inhibitors with good target potency and with low

174 eres resulted in several distinct classes of BACE-1 active site directed compounds with improved chem

175 ts a promising advance in the development of BACE-1 inhibitors.

176 e as a starting point for the development of BACE-1-directed Alzheimer's disease therapeutics.

177 inding pocket within the catalytic domain of BACE that is distinct from the enzymatic active site (i.

178 e, only (18)F-AV45 could detect an effect of BACE inhibitor treatment.

179 ine infusion protocol to evaluate effects of BACE inhibition on CNS APP processing by measuring the k

180 understanding of pharmacodynamic effects of BACE inhibition on NHP CNS, which can inform about targe

181 isms of cellular interactions and effects of BACE-1 inhibitors in AD.

182 The elevation of BACE enzymatic activity in AD is correlated with brain A

183 hemiluminescence assay for the evaluation of BACE-1 inhibition in cultured cells that assesses the le

184 Optimization of a first generation of BACE-1 inhibitors led to the discovery of novel hydroxye

185 data suggest that an age-related increase of BACE activity contributes to the increased production an

186 Abeta surrounding plaques, the inhibition of BACE activity can rescue neuronal hyperactivity, impaire

187 in AD brain, and suggest that inhibition of BACE may have a therapeutic effect in the prevention of

188 We hypothesized that CNS inhibition of BACE would result in decreased newly generated Abeta and

189 roduction of Abeta peptide, by inhibition of BACE, is an attractive therapeutic modality for the trea

190 Thus, blanket inhibition of BACE-1 function may have adverse side effects.

191 h-throughput screening for the inhibition of BACE-1.

192 Compound 14g is a potent inhibitor of BACE-1 with excellent permeability and a moderate P-gp l

193 ially selective small molecule inhibitors of BACE that act through exosite, rather than active site,

194 pyridine lead series to potent inhibitors of BACE-1 was demonstrated.

195 Inhibitors of BACE-1 with 3 muM to 32 nM potencies in cells are shown,

196 nsition state isostere derived inhibitors of BACE-1.

197 se hippocampal primary neurons, knockdown of BACE-1 almost completely blocks Egr-1-induced amyloidoge

198 activation and modest increases in levels of BACE 6 hours after anesthesia in mouse brain.

199 ism may explain increased cerebral levels of BACE and Abeta following cerebral ischemia and existing

200 caspase activation, and increases levels of BACE and Abeta up to 24 hours after anesthesia.

201 Ai silencing of GGA3 also elevated levels of BACE and Abeta.

202 Isoflurane increased the levels of BACE and gamma-secretase and secreted Abeta in the H4-AP

203 Levels of BACE-1 and sAPPbeta were significantly higher and of GDN

204 nversely correlated with increased levels of BACE.

205 The catalytic mechanism of BACE-1 requires water-mediated proton transfer from aspa

206 Here we show that the Drosophila ortholog of BACE, dBACE, is required for glial survival.

207 thiol-containing fragments versus a panel of BACE-1 active site cysteine mutants under redox-controll

208 The therapeutic potential of BACE will also be considered.

209 ntially important regions in the promoter of BACE, which may regulate its activity (1).

210 dynamics and inhibitor binding properties of BACE-1.

211 f 3765 nucleotides of the promoter region of BACE and 364 nucleotides of the 5' untranslated region o

212 Asp 228) present in the catalytic region of BACE that can adopt multiple protonation states.

213 ites constitutes the core promoter region of BACE.

214 Our findings reveal a negative regulation of BACE expression by physiological neuronal activity and a

215 Regulation of BACE may play an important role in regulating the levels

216 is not meant to be a comprehensive review of BACE.

217 The results point to a biological role of BACE in synapse function and plasticity as well as a pot

218 e nonprime side region of the active site of BACE-1, and extends toward the S3 subpocket (S3sp).

219 ation of the inhibitor in the active site of BACE-1.

220 The crystal structure of BACE in complex with this hydroxyethyl secondary amine i

221 We determined the apo structure of BACE to 1.75 A, and a structure of a hydroxyethylamine i

222 ne (ABP) moiety, X-ray crystal structures of BACE mutant-disulfide conjugates revealed that the fragm

223 for APP-related, protein-based substrates of BACE.

224 The carboxyl terminus of BACE contains a di-leucine-based signal for sorting of t

225 rscoring the potential multifaceted value of BACE-1 inhibition in AD therapeutics.

226 ced tau phosphorylation but has no effect on BACE-1 activation and amyloidogenic APP processing.

227 yzed whether sorLA interacts with APP and/or BACE.

228 The aspartyl protease beta-secretase, or BACE, has been demonstrated to be a key factor in the pr

229 ld-type (WT) and TG mice received vehicle or BACE inhibitor (60 mg/kg) starting at 7 wk of age.

230 nzymatic activity or the processing of other BACE substrates.

231 ulate BACE processing of APP but spare other BACE substrates and achieve therapeutic concentrations i

232 ity (K(i) = 17 pM) and high selectivity over BACE 2 (>7000-fold) and cathepsin D (>250000-fold).

233 Analysis of PDAPP/BACE(-/-) mice demonstrated that BACE1 is absolutely req

234 ogues, have been found to be brain penetrant BACE-1 inhibitors.

235 acts as a trafficking receptor that prevents BACE-APP interactions and hence BACE cleavage of APP.

236 A type I transmembrane aspartyl protease, BACE (beta-site APP cleaving enzyme), has been identifie

237 features of HS for inhibiting the protease, BACE-1.

238 discovered that sorLA significantly reduced BACE-APP interactions in Golgi.

239 flurane may increase BACE levels by reducing BACE degradation.

240 idated a GGA3-dependent mechanism regulating BACE levels and beta-secretase activity.

241 in AD brain, and increasing evidence reveals BACE as a stress-related protease that is upregulated fo

242 he generation of Abeta is the beta-secretase BACE, for which powerful inhibitors have been developed

243 Whether elevated beta-secretase (BACE) activity is related to plaque formation or amyloid

244 APP can be cleaved by beta-secretase (BACE) and alpha-secretase to produce APP-C99 and APP-C83

245 rylation, and decreases both beta-secretase (BACE) and APOEepsilon4 gene expression.

246 d precursor protein (APP) by beta-secretase (BACE) and gamma-secretase.

247 etic inhibitors of the human beta-secretase (BACE) are described.

248 es for use in SAR studies of beta-secretase (BACE) inhibitors and also as versatile ligands for other

249 Beta-secretase (BACE) is a critical enzyme in the production of beta-amy

250 beta-Secretase (BACE) is a prerequisite for amyloidogenesis, and it is u

251 d 3xTg-AD mice deficient for beta-secretase (BACE), the protease required for Abeta generation from A

252 inant APP as a substrate for beta-secretase (BACE), we have identified a series of compounds that inh

253 shedding of surface APP in a beta-secretase (BACE)-dependent manner.

254 of the validated AD targets beta-secretase (BACE-1) and glycogen synthase kinase-3beta (GSK-3beta) b

255 amidine-based inhibitors of beta-secretase (BACE-1).

256 ved inhibitors of the enzyme beta-secretase (BACE-1).

257 the aspartic acid protease, beta-secretase (BACE-1).

258 rs (the APP cleaving enzymes beta-secretase [BACE] and presenilin-1 [PS-1], and putative clearance mo

259 the di-leucine motif plays a role in sorting BACE to lysosomes.

260 osomal degradation, consequently stabilizing BACE and elevating Abeta generation.

261 This review summarizes BACE properties, describes BACE translation dysregulatio

262 di-leucine motif is necessary for targeting BACE to the lysosomes.

263 ed reduction of amyloid-beta pathology in TG-BACE mice.

264 Collectively, our data indicate that BACE is transported to the late endosomal/lysosomal comp

265 These results suggest that BACE and TACE share a common TGN localization, but under

266 ng only weak inhibitory activity against the BACE enzyme, the small compound was verified by biophysi

267 vealed by X-ray crystallography, between the BACE-1 catalytic diad and a weak NMR screening hit (3),

268 In contrast, the BACE-LL/AA mutant, in which Leu(499) and Leu(500) in the

269 t 100 microM inhibitor concentration for the BACE-1 enzyme revealed a novel spiropiperidine iminohyda

270 r BACE elevation was due to mutations in the BACE-coding region, we sequenced the entire ORF region o

271 n, we sequenced the entire ORF region of the BACE gene in these same AD and nondemented patients and

272 We found no mutations in the ORF of the BACE gene.

273 We present the genomic organization of the BACE gene.

274 eotides of the 5' untranslated region of the BACE mRNA (5' UTR).

275 ted the iBSEC1 scFv, since it recognizes the BACE-1 cleavage site on APP but does not bind the adjace

276 Surprisingly, the BACE-LRP interaction leads to an increase in LRP C-termi

277 Binding of peptides to the BACE exosite leads to a concentration-dependent inhibiti

278 rate that in COS-7 cells, Egr-1 binds to the BACE-1 promoter and activates BACE-1 transcription.

279 dissected the regulatory regions within the BACE promoter into areas containing positive and negativ

280 Thus, BACE is a prime drug target for the therapeutic inhibiti

281 hippocampal primary neurons, Egr-1 binds to BACE-1 and p35 promoters, enhances tau phosphorylation,

282 ucture of representative inhibitors bound to BACE-1 revealed a number of key ligand:protein interacti

283 Direct binding of GGA1 to BACE was not required for these effects, but the integri

284 -NRG1 and NRG3 that render them resistant to BACE cleavage, as well as BACE inhibition, result in the

285 ent binding free energy profiles for various BACE-1-inhibitor complexes.

286 ificantly reduced secreted Abeta levels when BACE was overexpressed, suggesting that sorLA influences

287 this study, we set out to determine whether BACE is degraded by the lysosomal pathway and whether th

288 To examine whether BACE elevation was due to mutations in the BACE-coding r

289 Understanding the mechanism by which BACE-1 is activated leading to Abeta synthesis in the br

290 While BACE-1 is sorted into acidic recycling endosomes, APP is

291 lved in BACE trafficking, are reduced, while BACE levels are increased.

292 erm pathological co-accumulation of APP with BACE, PS-1, and activated caspase.

293 alpha or enhancement of its association with BACE may be viable strategies to ameliorate imbalances i

294 Thus, sorLA interacts both with BACE and APP and might therefore directly affect BACE-AP

295 ional crystal structure of 7 in complex with BACE-1 revealed that the amino group of the inhibitor co

296 binding (GGA) protein family, interacts with BACE and influences its subcellular distribution.

297 e that the light chain of LRP interacts with BACE on the cell surface in association with lipid rafts

298 stions about the timing of intervention with BACE-1 inhibitors, and anti-amyloid therapies in general

299 s and eukaryotic pepsins, in particular with BACE-1, thereby confirming their phylogenetic proximity.

300 An X-ray cocrystal structure with BACE-1 revealed a novel mode of binding whereby the inhi

301 ne, noncovalent inhibition of wild-type (WT) BACE-1 activity.