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

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

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

12 of amyloid-beta precursor protein (APP) and presenilin 1 (PS1) as well as human apoA-I (AI).

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

51 lly active protein complexes with endogenous presenilin 1 and PEN2 or affect the localization of gamm

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

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

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

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

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

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

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

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

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

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

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

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

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

65 minent amyloid deposition in the striatum in presenilin 1 mutation carriers.

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

67 A few individuals with presenilin 1 mutations showed increased cerebellar (11)C

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

87 )-4 gene in beta-amyloid precursor protein + presenilin-1 (APP+PS1) bigenic mice attenuates AD pathog

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

106 the Alzheimer's disease (AD)-related protein presenilin-1 (PS1).

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

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

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

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

111 ve identified 2 new sequence variants in the presenilin-1 (PSEN1) gene promoter leading to reduced ge

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

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

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

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

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

117 Mutations in presenilin-1 and presenilin-2 (PS1 and PS2) are the most

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

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

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

121 We also show that presenilin-1 coimmunoprecipitates with SERCA2a.

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

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

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

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

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

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

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

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

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

131 zheimer's disease caused by the E280A single presenilin-1 mutation, thirty carriers of the mutation w

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

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

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

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

136 man, including human-specific correlation of presenilin-1 with oligodendrocyte markers, and significa

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

138 Dysfunction of presenilin-1, misprocessing of amyloid precursor protein

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

140 osomal acidification caused by dysfunctional presenilin-1.

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

142 0 (ADAM10) and the gamma-secretase component presenilin-1.

143 ine whether gamma-secretase modulators alter Presenilin-1/gamma-secretase conformation in intact cell

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

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

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

147 We conclude that mutations in presenilin 2 are rare with only seven being well documen

148 ploinsufficiency as pathogenic mechanisms in presenilin 2 associated Alzheimer's disease.

149 and reviewed the world's literature on other presenilin 2 mutations; presenting a novel mutation that

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

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

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

153 Mutations in presenilin-1 and presenilin-2 (PS1 and PS2) are the most common cause of

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

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

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

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

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

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

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

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

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

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

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

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

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

167 Presenilin and nicastrin are both indispensable componen

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

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

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

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

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

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

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

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

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

177 moothened and the Notch pathway genes Notch, presenilin, and Suppressor of Hairless and the Enhancer

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

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

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

181 Mutations in presenilins are linked to familial autosomal dominant Al

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

183 Presenilins are proteins with nine transmembrane (TM) do

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

185 Presenilins are ubiquitous, intramembrane proteins that

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

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

188 K1 interacts with the mitochondrial protease presenilin-associated rhomboid-like protein (PARL) and t

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

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

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

192 The presenilin-containing gamma-secretase complex produces t

193 Presenilin-deficient cells inefficiently clear long-live

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

215 pathogenic mutations cause a general loss of presenilin function.

216 n these results, we previously proposed that presenilins function as endoplasmic reticulum (ER) passi

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

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

219 Familial AD (FAD) mutations in presenilins have been linked to calcium (Ca(2+)) signali

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

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

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

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

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

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

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

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

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

229 suggested that CBP might be a key target of presenilins in the regulation of memory formation and ne

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

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

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

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

234 precursor protein Swedish mutant transgene, presenilin knock-in mutation, and tau P301L mutant trans

235 o axonal transport defects in the context of presenilin loss, we used a mouse model postnatally defic

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

237 hat disruption of ER Ca(2+) leak function of presenilins may play an important role in AD pathogenesi

238 overed that, in hippocampal neurons, loss of presenilin-mediated ER Ca(2+) leak function was compensa

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

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

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

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

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

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

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

246 ubiquitous, multiprotein enzyme composed of presenilin, nicastrin, Aph-1, and Pen-2.

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

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

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

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

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

252 The human genome codes for two presenilin paralogs.

253 Interestingly, we discovered that presenilins play a major role in ER Ca(2+) leak function

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

255 Presenilins play essential roles in memory formation, sy

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

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

258 ction of Abeta42 as an essential property of presenilin proteins bearing pathogenic mutations.

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

260 butable to mutations in a single copy of the Presenilin (PS) and amyloid precursor protein genes.

261 tological clues have implicated the proteins presenilin (PS) and tau as key players in AD development

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

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

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

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

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

267 four components of gamma-secretase complex--presenilin (PS), nicastrin (NCT), Pen2, and Aph1--are al

268 our integral transmembrane protein subunits: presenilin (PS), nicastrin, APH1, and PEN2.

269 includes the aspartyl intramembrane protease presenilin (PS).

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

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

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

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

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

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

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

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

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

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

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

281 Presenilin (PSEN) deficiency is accompanied by accumulat

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

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

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

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

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

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

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

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

290 Studies of FAD-linked forms of presenilin (psn) in model organisms, however, indicate t

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