ライフサイエンスコーパス: presenilin

1 milarly modulated by the presence/absence of presenilins.

2 (2+)-leak mechanisms, namely translocons and presenilins.

3 eolytic processing, first by Adam10 and then presenilins.

4 f axonal boutons and dendritic spines in APP/Presenilin 1 (APP(swe)/PS1(L166P))-green fluorescent pro

5 icular infusion in amyloid precursor protein/presenilin 1 (APP/PS1) double-transgenic 3-mo-old mice a

6 athology using the amyloid precursor protein/presenilin 1 (APP/PS1) mouse model of AD amyloidosis on

7 LTP impairments in amyloid precursor protein/presenilin 1 (APP/PS1) mutant mice that model Alzheimer'

8 at overexpress amyloid precursor protein and presenilin 1 (APP/PS1).

9 mutated human amyloid precursor protein and presenilin 1 (APP/PS1-Tg).

10 double mutant amyloid precursor protein and presenilin 1 (APPswe/PSEN1dE9) mouse model of Alzheimer'

11 PEDF up-regulation of full-length presenilin 1 (Fl.PS1) facilitated the association of vas

12 Missense mutations in presenilin 1 (PS1) and presenilin 2 (PS2) proteins are a

13 T Inheritance of mutations in genes encoding presenilin 1 (PS1) causes familial Alzheimer's disease (

14 how that amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic (APP/PS1) mice demo

15 We demonstrated that presenilin 1 (PS1) endocytosis requires interaction with

16 In APP mice, mutant presenilin 1 (PS1) enhances generation of Abeta42 and in

17 terminal fragment (betaCTF), and then by the Presenilin 1 (PS1) enzyme in the gamma-secretase complex

18 ent induced a decrease in the association of presenilin 1 (PS1) fragments with lipid rafts where cata

19 Mutations in the presenilin 1 (PS1) gene lead to early-onset Alzheimer's

20 Presenilin 1 (PS1) has been implicated in apoptosis; how

21 ic ablation studies have revealed a role for presenilin 1 (PS1) in embryonic neurogenesis, little inf

22 Presenilin 1 (PS1) is an essential gamma-secretase compo

23 Presenilin 1 (PS1) is an integral component of gamma-sec

24 Presenilin 1 (PS1) is the catalytic subunit of gamma-sec

25 In in vivo studies on wild-type and APP/presenilin 1 (PS1) mice, two selected compounds were wel

26 Presenilin 1 (PS1) mutations are the most common cause o

27 ne (S) and threonine (T) residues within the Presenilin 1 (PS1) N-terminus and in the large hydrophil

28 on in transgenic male mice expressing mutant presenilin 1 (PS1) or PS1(M146V/+) "knock-in" mice leads

29 MRK-560 displays a strong preference for the presenilin 1 (PS1) over PS2 subclass of gamma-secretases

30 ion (GD) conditions, decreased expression of presenilin 1 (PS1) results in decreased neuronal surviva

31 Here we show that absence of presenilin 1 (PS1) results in dramatic decrease (>95%) o

32 Accordingly, Abeta deposition in APP and presenilin 1 (PS1) transgenic mice is significantly redu

33 CXCR3 in the amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mouse model of AD.

34 Using the amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mouse model, we found that

35 of amyloid beta precursor protein (APP) and presenilin 1 (PS1) with AD mutations, we show that patho

36 e male amyloid precursor protein (APP)(SWE) /presenilin 1 (PS1)(DeltaE9) transgenic model of Abeta am

37 ransmembrane domains (TMDs) 4 and 5 of human presenilin 1 (PS1), a catalytic subunit of gamma-secreta

38 The gamma-secretase complex, comprising presenilin 1 (PS1), PEN-2, APH-1 and nicastrin, is a mem

39 Presenilin 1 (PS1), the catalytic subunit of the gamma-s

40 gamma-Secretase, or its catalytic subunit presenilin 1 (PS1), were upregulated by exposure to eith

41 r's disease mapping to the catalytic subunit presenilin 1 (PS1).

42 f mutant presenilin 1 genes (PSEN1) encoding presenilin 1 (PS1)variants causes autosomal dominant for

43 human amyloid precursor protein (APPsw) and presenilin 1 (PS1DeltaE9) genes, each independent causes

44 ippocampal neurons derived from mice lacking presenilin 1 (Psen1(-/-) mice) or expressing a familial

45 in amyloid precursor protein (APP(Swe)) and presenilin 1 (PSEN1(M146V)) and derived cortical neurons

46 gin to differentiate between carriers of the presenilin 1 (PSEN1) E280A (Glu280Ala) mutation and age-

47 -related accumulation of Abeta deposition in presenilin 1 (PSEN1) E280A mutation carriers across the

48 een January and August, 2010, 18-26-year-old presenilin 1 (PSEN1) E280A mutation carriers and non-car

49 Presenilin 1 (Psen1) is important for vascular brain dev

50 Whereas, distinct presenilin 1 (PSEN1) mutations lead to either (2) reduce

51 gamma-secretase complex: nicastrin (NCSTN), presenilin 1 (PSEN1), presenilin enhancer 2 (PSENEN) and

52 ations in amyloid precursor protein (APP) or presenilin 1 (PSEN1), sporadic Alzheimer's disease (n =

53 eferred to as ABCC1), we measured N1(IC) and presenilin 1 (PSEN1), the catalytic subunit of gamma-sec

54 store-operated Ca(2+) entry (SOCE) due to a presenilin 1 (PSEN1)-dependent reduction in ER Ca(2+) le

55 biomarkers are characterized and compared in presenilin 1 (PSEN1)E280A mutation carriers and noncarri

56 t, it resulted in a significant reduction of presenilin 1 (PSEN1, alias PS1), nicastrin (NCSTN) , pre

57 ial AD (FAD; amyloid precursor protein [APP]/presenilin 1 [PS1]) ameliorated the autophagocytic defec

58 utations in amyloid precursor protein (APP), presenilin 1 and 2 (PSEN1 and PSEN2) cause a subset of e

59 nic mice with human familial mutant genes of presenilin 1 and amyloid precursor protein (PS1/APP), th

60 ums of mice expressing human familial mutant presenilin 1 and amyloid precursor protein genes, the le

61 s mutant human amyloid precursor protein and presenilin 1 and followed the death of individual neuron

62 ditional knock-out mouse studies showed that Presenilin 1 and Notch 1 controlled neural sphere format

63 , Abeta40, and Abeta42) but has no effect on presenilin 1 and presenilin 2.

64 ations in beta-amyloid precursor protein and presenilin 1 are able to induce robust extracellular dep

65 WT) mice and 9 amyloid precursor protein and presenilin 1 double-transgenic (APPswe/PS1DeltaE9 [APP/P

66 he gamma-secretase and the redistribution of presenilin 1 from lipid rafts.

67 RNA and component of gamma-secretase complex presenilin 1 from Tsc1-null cells to wild-type cells lea

68 me that this disorder can stem from aberrant presenilin 1 function.

69 Inheritance of mutant presenilin 1 genes (PSEN1) encoding presenilin 1 (PS1)va

70 of understanding the structural dynamics of presenilin 1 in drug development against Alzheimer's dis

71 D mutations in amyloid precursor protein and presenilin 1 leads to sensitivity to trauma-induced PTSD

72 -methylcytosine in amyloid precursor protein/presenilin 1 mice along with Alzheimer disease pathology

73 of DSP-8658 in the amyloid precursor protein/presenilin 1 mouse model confirmed an increased microgli

74 uded; 18 were positive for the AD-associated presenilin 1 mutation (carriers, mean age=38) whereas 22

75 Compared to non-carriers, presymptomatic presenilin 1 mutation carriers exhibited thinner cortex

76 A cohort of 20 presenilin 1 mutation carriers underwent volumetric and

77 encoding the wild-type AbetaPP and the L166P presenilin 1 mutation.

78 en seen to interact with the gamma-secretase presenilin 1 subunit (PS1).

79 mational changes in transmembrane domains of presenilin 1 that affect the proteolytic activity of the

80 ne substitutions in the prion protein and in presenilin 1 that underlie the development of a prion di

81 ent chaperone, cyclophilin B, from assisting presenilin 1 to fold properly, leading to its aggregatio

82 tration of bifunctionalized liposomes to APP/presenilin 1 transgenic mice (aged 10 months) for 3 week

83 reduced quantities of the processed, active presenilin 1 were observed in brains of cyclophilin B kn

84 g proteins, and prevented the association of presenilin 1 with N-cadherin and VE-cadherin, thereby co

85 rexpression of amyloid precursor protein and presenilin 1 with Swedish and L166P mutations, respectiv

86 We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest

87 essing human amyloid-beta precursor protein, presenilin 1, and tau mutations, and apolipoprotein E, t

88 onverting enzyme, amyloid precursor protein, presenilin 1, neprylisin or insulin-degrading enzyme.

89 DLL1,3,4), gamma-secretase complex proteins (Presenilin 1, Nicastrin), and downstream target Hes-1.

90 Abeta42) by around 70%, whereas knockdown of presenilin 1, one of the essential gamma-secretase compl

91 l AD (FAD), are associated with mutations in presenilin 1, presenilin 2, or the amyloid precursor pro

92 on of Abeta(42/43) by familial AD mutants of presenilin 1, the catalytic subunit of gamma-secretase,

93 nt from plaques in amyloid precursor protein/presenilin 1-GFP (APPPS1-GFP) nor those in GFP-control m

94 id precursor protein, with or without mutant presenilin 1.

95 pain, potassium channel activity, and binds presenilin 1.

96 familial Alzheimer's disease or mutations in presenilin 1.

97 mplex composed of Aph1, Pen2, Nicastrin, and Presenilin 1.

98 FAD can also result from mutations in the presenilin 1/2 (PSEN1/2) genes, whose protein products p

99 Presenilins 1 and 2 (PS1 and 2) are the catalytic subuni

100 Presenilins 1 and 2 (PS1 and PS2) are the catalytic subu

101 es in a late-stage amyloid precursor protein/presenilin-1 (APP/PS-1) human transgenic double-knock-in

102 etion in older age amyloid precursor protein/presenilin-1 (APP/PS1) mice.

103 ressing mutant amyloid precursor protein and presenilin-1 (APP/PS1) were crossed with Ear2(-/-) mice

104 g mutant human amyloid precursor protein and presenilin-1 (APP/PS1).

105 u(P301L)), and physiological levels of M146V-presenilin-1 (PS1(M146V)) display extracellular amyloid-

106 Mutations in the gene encoding presenilin-1 (PS1) are found in approximately 80% of cas

107 Mutations in the PSEN1 gene encoding Presenilin-1 (PS1) are the predominant cause of familial

108 igate the impact of the c.548G>T mutation on presenilin-1 (PS1) function in vivo, we introduced this

109 (average age 33.7 years) who carry the E280A presenilin-1 (PS1) genetic mutation for FAD.

110 Presenilin-1 (PS1) is a multifunctional protein involved

111 Presenilin-1 (PS1) is the catalytic core of the aspartyl

112 Presenilin-1 (PS1) is the catalytic subunit of gamma-sec

113 red that, in amyloid precursor protein (APP)/presenilin-1 (PS1) mice (age 3-4 mo), a prominent mouse

114 ut mice with amyloid precursor protein (APP)/presenilin-1 (PS1) mice overexpressing mutant APP and PS

115 Here, we report that presenilin-1 (PS1) null mouse cortical neuronal cultures

116 amyloid-beta precursor protein (AbetaPP) and presenilin-1 (PS1) recapitulate several aspects of this

117 ntly improves the cognitive functions of APP/presenilin-1 (PS1) transgenic mice.

118 eta-amyloid (Abeta) precursor protein (APP), presenilin-1 (PS1), and presenilin-2.

119 trin (NCT) in the extracellular (EC) domain, presenilin-1 (PS1), anterior pharynx defective 1, and pr

120 We show that presenilin-1 (PS1)/gamma-secretase is required for axon

121 ecifically labels the N-terminal fragment of presenilin-1 (PS1-NTF) in cell membranes as well as in l

122 mutant amyloid precursor protein (APPsw) and presenilin-1 (PS1DeltaE9) was characterized for histolog

123 Loss of presenilin-1 (PSEN1) function causing AD impedes acidifi

124 Mutations in the presenilin-1 (PSEN1) gene are associated with familial A

125 Mutations in the Presenilin-1 (PSEN1) gene are the major cause of familia

126 l dominant, highly penetrant mutation in the presenilin-1 (PSEN1) gene, and performed genome-wide ass

127 of the fully penetrant E280A mutation in the presenilin-1 (PSEN1) gene.

128 We recently reported that homozygous Presenilin-1 (Psen1) knockin (KI) mice carrying the fami

129 ral interneurons in Columbus mutants lacking Presenilin-1 acquire an inappropriate attraction to Netr

130 We recently showed that presenilin-1 and -2, the catalytic components of gamma-s

131 revent the hyperoxia-induced dissociation of presenilin-1 and presenilin-1-associated protein to atte

132 or protein or the gamma-secretase components presenilin-1 and presenilin-2 that cause familial early-

133 roximal CRE/TATA-less promoters (e.g. Nr4a3, Presenilin-1 and Presenilin-2).

134 livered bilaterally to the hippocampi of APP+presenilin-1 bigenic mice via an adenoassociated virus s

135 ge on cortical neuron survival by generating presenilin-1 conditional knock-out (PS1 cKO) mice carryi

136 idence that elastase increased intracellular presenilin-1 expression through PAR-2 signaling.

137 hat FAD mutations can cause complete loss of Presenilin-1 function in vivo, suggesting that clinical

138 We mapped this mutation to the Presenilin-1 gene.

139 The Presenilin-1 group had similar parietal involvement to t

140 of beta-amyloid precursor protein (APP) and presenilin-1 leads to a significant inhibition of neurog

141 hroom spines in hippocampal neurons from the presenilin-1 M146V knockin (KI) mouse model of familial

142 itor dantrolene to amyloid precursor protein-presenilin-1 mice (Thy1-APP(KM670/671NL), Thy1-PS1(L166P

143 el expressing the Swedish mutant APP and the presenilin-1 mutant DeltaE9 reduces amyloid plaque load,

144 milial Alzheimer disease (FAD) patients with presenilin-1 or -2 mutations exhibit altered processing

145 al organoids bearing AD-related mutations in presenilin-1 or amyloid precursor protein vs. isogenic g

146 is of five different AD-causing mutations in presenilin-1 revealed that all result in drastic reducti

147 essing mutated amyloid precursor protein and presenilin-1 that develop massive cerebral Abeta loads.

148 n amyloid precursor protein and mutant human presenilin-1 transgenes).

149 l components of the gamma-secretase complex, presenilin-1, -2, and nicastrin, accumulate in the mitoc

150 protein components (Aph-1, Pen-2, nicastrin, presenilin-1, or presenilin-2) of the gamma-secretase in

151 xia-induced dissociation of presenilin-1 and presenilin-1-associated protein to attenuate poly ADP-ri

152 osomal acidification caused by dysfunctional presenilin-1.

153 endent-interacting protein 1, clusterin, and presenilin-1.

154 0 (ADAM10) and the gamma-secretase component presenilin-1.

155 Missense mutations in presenilin 1 (PS1) and presenilin 2 (PS2) proteins are a major cause of familia

156 lular Abeta40 were abolished by depletion of presenilin 2 (PSEN2), recently shown to be enriched on t

157 Mutations in presenilin 2 are rare causes of early onset familial Alz

158 cursor protein processing enzymes (BACE1 and presenilin 2) and are accompanied by elevated Abeta pept

159 e associated with mutations in presenilin 1, presenilin 2, or the amyloid precursor protein.

160 eta42) but has no effect on presenilin 1 and presenilin 2.

161 neuroblastoma cell line containing familial presenilin-2 AD mutation.

162 Extending this correlation, we find that Presenilin-2 localizes to basal bodies/cilia through a c

163 When this motif is mutated, a GFP-tagged Presenilin-2 still localizes to intercellular borders, b

164 gamma-secretase components presenilin-1 and presenilin-2 that cause familial early-onset AD.

165 s (Aph-1, Pen-2, nicastrin, presenilin-1, or presenilin-2) of the gamma-secretase in HEK293 cells.

166 less promoters (e.g. Nr4a3, Presenilin-1 and Presenilin-2).

167 ursor protein (APP), presenilin-1 (PS1), and presenilin-2.

168 The interaction of Sanpodo with Presenilin, a component of the gamma-secretase complex,

169 Both are in the same GxGD family as presenilin, a protein mutated in Alzheimer Disease.

170 ndings show that partial to complete loss of presenilin activity causes progressively more severe neu

171 suggest that dominant-negative inhibition of presenilin activity plays an important role in FAD patho

172 In addition to gamma-secretase function, presenilins also demonstrate a low conductance endoplasm

173 Alzheimer's-causing mutations in presenilin altered the Abeta42/40 peptide ratio generate

174 inding that genetic deletion or knockdown of presenilins alters many autophagy-related proteins demon

175 Presenilin and nicastrin are both indispensable componen

176 We previously demonstrated that presenilin and nicastrin, components of the gamma-secret

177 d nicastrin, triggers the endoproteolysis of presenilin and results in an active tetrameric gamma-sec

178 gellin peptidase, type 4 prepilin peptidase, presenilin and signal peptide peptidase.

179 ermediate, composed of the catalytic subunit presenilin and the accessory proteins APH-1 (anterior ph

180 omain, consistent with the known presence of presenilins and gamma-secretase activity in rafts.

181 a and neurotrypsin as new genes repressed by presenilins and reveals a novel mechanism used by presen

182 nts a new layer of regulation that links the presenilins and the gamma-secretase protease to pro-infl

183 ', including mitsugumin23 (MG23), pannexins, presenilins and the transient receptor potential (TRP) c

184 ', including mitsugumin23 (MG23), pannexins, presenilins and the transient receptor potential (TRP) c

185 The gamma-secretase complex, composed of presenilin, anterior-pharynx-defective 1, nicastrin, and

186 to bacterial pathogenesis, and mutations in presenilin are associated with Alzheimer's disease.

187 Familial AD mutations in presenilin are known to exacerbate lysosomal pathology.

188 Mutations in presenilins are linked to familial autosomal dominant Al

189 ings, we conclude that endogenous, wild-type presenilins are necessary for proper protein degradation

190 Presenilins are proteins with nine transmembrane (TM) do

191 In later stages, downstream of Notch, the Presenilins are still required to maintain the endocrine

192 Presenilins are ubiquitous, intramembrane proteins that

193 VEGFR1 signaling and identified full-length presenilin as a critical adaptor molecule in the dephosp

194 ctivity is independent from that of Oma1 and presenilin-associated rhomboid-like (PARL), two known Op

195 e that the small GTPase ARF4 is required for Presenilin basal body localization, Notch signaling, and

196 gosomes are enriched for nicastrin, APH, and presenilin components of gamma-secretase, a multimeric p

197 Alzheimer's disease-linked presenilin genes (presenilin conditional double knockout [PS cDKO]) after

198 The presenilin-containing gamma-secretase complex produces t

199 Presenilin-deficient cells inefficiently clear long-live

200 effector RBP-Jkappa with lineage tracing in Presenilin-deficient endocrine progenitors, demonstrated

201 nt and wild-type PS1 at equal gene dosage in presenilin-deficient mouse embryo fibroblasts resulted i

202 Our findings reveal that Presenilin-dependent DCC receptor processing coordinates

203 Overall, these novel constructs unravel a presenilin-dependent subcellular targeting of gamma-secr

204 ison of the crystal structure with models of presenilin derived from biochemical analysis reveals thr

205 ase components, (3) reducing cholesterol and presenilin distribution in lipid rafts implicated in amy

206 his study, we examine the effects of varying presenilin dosage on cortical neuron survival by generat

207 h primary neuronal cultures from conditional presenilin double-knock-out mice (PS1(dTAG/dTAG), PS2(-/

208 nx-defective 1 (APH-1), nicastrin (NCT), and presenilin enhancer 2 (PEN-2) is of significant therapeu

209 (PSEN, catalytic subunit), Nicastrin (NCT), Presenilin Enhancer 2 (PEN-2), and Anterior Pharynx Defe

210 ), anterior pharynx-defective 1 (APH-1), and presenilin enhancer 2 (PEN-2), is assembled in a highly

211 anterior pharynx-defective 1 (APH1) but not presenilin enhancer 2 (PEN2).

212 ex: nicastrin (NCSTN), presenilin 1 (PSEN1), presenilin enhancer 2 (PSENEN) and in POGLUT1, an endopl

213 in 1 (PSEN1, alias PS1), nicastrin (NCSTN) , presenilin enhancer 2 homolog (PSNEN, alias, Pen-2), and

214 n-1 (PS1), anterior pharynx defective 1, and presenilin enhancer 2 in the transmembrane (TM) domain.

215 The incorporation of PEN-2 (presenilin enhancer 2) into a pre-activation intermediat

216 me complex comprising presenilin, nicastrin, presenilin enhancer 2, and anterior pharynx-defective 1

217 anterior-pharynx-defective 1, nicastrin, and presenilin enhancer 2, catalyzes the intramembranous pro

218 ous truncating mutations in PSENEN, encoding presenilin enhancer protein 2, in 6 unrelated patients a

219 odel systems, we show that in the absence of presenilin expression and gamma-secretase activity, TNF-

220 the L435F and C410Y mutations cause loss of Presenilin function and gamma-secretase activity, includ

221 ortex during aging, suggesting that impaired presenilin function by PSEN mutations may lead to neurod

222 mutation results in a brain-specific loss of presenilin function due to decreased Psen1 mRNA expressi

223 oteolysis of transmembrane substrates by the presenilin-gamma-secretase complex is preceded and regul

224 tch1 and/or Notch2 are functional targets of presenilin/gamma-secretase in promoting survival of exci

225 mice lacking the Alzheimer's disease-linked presenilin genes (presenilin conditional double knockout

226 posal that higher-order proteases, including presenilin, have channel function.

227 show that lipids in annular positions on the presenilin homologue protease are subject to constant ex

228 The presenilin homologue signal-peptide-peptidase-like 2a (S

229 oss of neuronal connections, but the role of Presenilin in establishing neuronal connections is less

230 The role of presenilins in autophagy has many implications for its f

231 mpact autophagy, indicating that the role of presenilins in autophagy is independent of gamma-secreta

232 olog Prss12 as genes negatively regulated by presenilins in Drosophila larval brains and mouse embryo

233 Complete inactivation of presenilins in excitatory neurons of the adult mouse cer

234 To directly investigate the role of presenilins in neuronal ER Ca(2+) homeostasis, we here p

235 ely, our studies fail to document a role for presenilins in regulating cellular autophagosomal functi

236 We hypothesized that mutant presenilins increase cellular vulnerability to stress.

237 Mutations in presenilins increase ratios of 42- to 40-residue Abeta c

238 Thus, Presenilin is a key neural circuit builder that gates th

239 The water-filled cavity within presenilin is necessary to mediate the intramembrane pro

240 The Alzheimer's disease-linked gene presenilin is required for intramembrane proteolysis of

241 sis that the hydrophilic catalytic cavity of presenilins may also constitute a Ca(2+) conductance por

242 respectively-are increased significantly in presenilin-mutant cells and in fibroblasts from patients

243 Using gamma-secretase drug inhibitors and presenilin mutants in mouse embryonic fibroblasts, we fo

244 through intramembrane proteolysis, and >100 presenilin mutations are associated with familial early-

245 unction, and many familial Alzheimer disease presenilin mutations impair this function.

246 be, we demonstrated specific labeling of the presenilin N-terminal fragment (PS1-NTF) within the gamm

247 eric membrane-embedded protease comprised of presenilin, nicastrin (NCT), anterior pharynx defective

248 The gamma-secretase complex, composed of presenilin, nicastrin (NCT), anterior pharynx-defective

249 cretase is a large enzyme complex comprising presenilin, nicastrin, presenilin enhancer 2, and anteri

250 gether, these findings show that, similar to presenilins, nicastrin plays essential roles in the regu

251 -related neurodegeneration caused by loss of presenilin or gamma-secretase and suggest that there is

252 of age, whereas conditional inactivation of presenilin or nicastrin using the same alphaCaMKII-Cre t

253 ta42/Abeta40 ratios, with minimal effects on presenilin or the Notch1 pathway in the brain.

254 The human genome codes for two presenilin paralogs.

255 challenge this idea and propose instead that presenilins play a role in calcium-mediated lysosomal fu

256 Presenilins play essential roles in memory formation, sy

257 elucidate the function endogenous, wild-type presenilins play in autophagy-mediated protein degradati

258 ariy attributable to mutations in one of two presenilins, polytopic proteins that contain the catalyt

259 iest pathophysiological indicators in mutant presenilin (PS) AD mice is increased intracellular Ca(2+

260 disease (FAD) is linked to mutations in the presenilin (PS) homologs.

261 Alzheimer's disease (AD)-linked presenilin (PS) mutations result in pronounced endoplasm

262 Presenilin (PS) plays a central role in the pathogenesis

263 We previously showed that presenilin (PS), a gene involved in Alzheimer's disease

264 of the gamma-secretase complex consisting of presenilin (PS), anterior pharynx-defective 1 (APH-1), n

265 includes the aspartyl intramembrane protease presenilin (PS).

266 amyloid precursor protein (APP), or APP and presenilin (PS).

267 BACE1 and presenilin (PS)/gamma-secretase play a major role in Alz

268 eractions between the C-terminal fragment of presenilin (PS-CTF), the central component of the gamma-

269 Mutations in presenilins (PS) account for most early-onset familial A

270 E STATEMENT To gain insight into the role of presenilins (PS) in excitatory synaptic function, we add

271 ial Alzheimer's disease (FAD)-causing mutant presenilins (PS) interact with inositol 1,4,5-trisphosph

272 Previous studies have shown that presenilins (PS), components of the gamma-secretase comp

273 Mutations in presenilins (PS), transmembrane proteins encoding the ca

274 , nicastrin and PEN2, and two variable ones, presenilin (PS1 or PS2) and APH1 (APH1aL, APH1aS, or APH

275 The complex is composed of presenilin (PS1 or PS2), anterior pharynx defect-1 (APH-

276 MDs) present in its four subunits, including presenilin (PS1 or PS2), the gamma-secretase catalytic c

277 Presenilin (PSEN) 1 and 2 are the catalytic components o

278 Presenilin (PSEN) deficiency is accompanied by accumulat

279 e familial Alzheimer's disease (FAD) causing presenilin (PSEN) mutations PSEN1-L435F and PSEN1-C410Y

280 tions in amyloid precursor protein (APP) and presenilin (PSEN) to familial Alzheimer's disease (AD) i

281 Presenilin (PSEN, catalytic subunit), Nicastrin (NCT), P

282 Alzheimer's disease (AD)-linked mutations in Presenilins (PSEN) and the amyloid precursor protein (AP

283 integrin and metalloproteinases (Adams), and presenilins (Psen).

284 Mutations in the presenilin (PSEN1 and PSEN2) genes are linked to familia

285 s in the amyloid precursor protein (APP) and presenilin (PSEN1 and PSEN2) genes.

286 Mutations in the presenilin (PSEN1, PSEN2) and amyloid precursor protein

287 encoding amyloid precursor protein (APP) or presenilins (PSEN1 or PSEN2) carrying mutations linked t

288 ecretase complexes, including two homologous presenilins (PSENs).

289 idence include the amyloid cascade (ACH) and presenilin (PSH) hypotheses and the amyloid precursor pr

290 o interacts molecularly and genetically with Presenilin (Psn) and other components of the gamma-secre

291 ial Alzheimer's disease (FAD)-causing mutant presenilins (PSs).

292 tase complex, but it remains unknown whether presenilin regulates synaptic function in a gamma-secret

293 Mutations in the presenilins that cause familial Alzheimer's disease alte

294 e proteases SPPL2a/b/c and SPPL3, as well as presenilin, the catalytic subunit of the gamma-secretase

295 Presenilins, the catalytic components of the gamma-secre

296 um (Ca(2)(+)) homeostasis has been linked to presenilins, the catalytic core in gamma-secretase compl

297 Presenilins, the major gene products involved in familia

298 nilins and reveals a novel mechanism used by presenilins to modulate CREB signaling based on controll

299 urther exacerbated by AD-linked mutations in presenilins to promote opening of IP(3) receptor/channel

300 Presenilins, which constitute the active center of the g