| We propose a model that identifies critical TMDs of Aph-1 for associations with Nct and PS for the stepwise assembly of gamma-secretase components. | Specific domains in anterior pharynx-defective 1 determine its intramembrane interactions with nicastrin and presenilin.
Chiang PM, Fortna RR, Price DL, Li T, Wong PC., Free PMC Article | 07/29/2022 |
| Aberrant role of pyruvate kinase M2 in the regulation of gamma-secretase and memory deficits in Alzheimer's disease. | Aberrant role of pyruvate kinase M2 in the regulation of gamma-secretase and memory deficits in Alzheimer's disease.
Han J, Hyun J, Park J, Jung S, Oh Y, Kim Y, Ryu SH, Kim SH, Jeong EI, Jo DG, Park SH, Jung YK. | 02/19/2022 |
| Assembly of gamma-secretase occurs through stable dimers after exit from the endoplasmic reticulum. | Assembly of γ-secretase occurs through stable dimers after exit from the endoplasmic reticulum.
Wouters R, Michiels C, Sannerud R, Kleizen B, Dillen K, Vermeire W, Ayala AE, Demedts D, Schekman R, Annaert W., Free PMC Article | 11/13/2021 |
| This work provides novel evidence for the role of miRNAs in memory formation and demonstrates the implication of APH1a protein in miRNA processing in the adult brain. | miR-151-5p modulates APH1a expression to participate in contextual fear memory formation.
Xu XF, Wang YC, Zong L, Wang XL., Free PMC Article | 04/13/2019 |
| Prostaglandin I2 accumulation in neuronal cells activates PKA/CREB and JNK/c-Jun signaling pathways by phosphorylation, which results in APH-1alpha/1beta expression. | Prostaglandin I2 upregulates the expression of anterior pharynx-defective-1α and anterior pharynx-defective-1β in amyloid precursor protein/presenilin 1 transgenic mice.
Wang P, Guan PP, Guo JW, Cao LL, Xu GB, Yu X, Wang Y, Wang ZY., Free PMC Article | 06/10/2017 |
| Thus, Leda-1/Pianp is constitutively processed by proprotein convertases, sheddases including MMPs and ADAM10/17 and intramembrane protease gamma-secretase. | Posttranslational proteolytic processing of Leda-1/Pianp involves cleavage by MMPs, ADAM10/17 and gamma-secretase.
Biswas S, Adrian M, Weber J, Evdokimov K, Winkler M, Géraud C. | 05/20/2017 |
| Abeta oligomers in the cerebrospinal fluid (CSF) further promoted the expression of APH-1alpha/-1beta (by >2.5-fold), which enhances the gamma-cleavage of APP and Abeta deposition during AD progression | By suppressing the expression of anterior pharynx-defective-1α and -1β and inhibiting the aggregation of β-amyloid protein, magnesium ions inhibit the cognitive decline of amyloid precursor protein/presenilin 1 transgenic mice.
Yu X, Guan PP, Guo JW, Wang Y, Cao LL, Xu GB, Konstantopoulos K, Wang ZY, Wang P. | 05/28/2016 |
| Upregulation of PS1/gamma-secretase activity may be a risk factor for late onset sporadic Alzheimer's disease. | Increased expression of PS1 is sufficient to elevate the level and activity of γ-secretase in vivo.
Li T, Li YM, Ahn K, Price DL, Sisodia SS, Wong PC., Free PMC Article | 02/7/2014 |
| ficiency of beta-arrestin1 or inhibition of binding of beta-arrestin1 with APH-1 by small peptides reduced Abeta production without affecting Notch processing | β-arrestin1 regulates γ-secretase complex assembly and modulates amyloid-β pathology.
Liu X, Zhao X, Zeng X, Bossers K, Swaab DF, Zhao J, Pei G., Free PMC Article | 09/7/2013 |
| Pen-2, as well as nicastrin and Aph-1alpha, is dispensable for presenilin endoproteolysis | Pen-2 is dispensable for endoproteolysis of presenilin 1, and nicastrin-Aph subcomplex is important for both γ-secretase assembly and substrate recruitment.
Mao G, Cui MZ, Li T, Jin Y, Xu X., Free PMC Article | 01/12/2013 |
| Aph-1 associates directly with full-length and C-terminal fragments of gamma-secretase substrates | Aph-1 associates directly with full-length and C-terminal fragments of gamma-secretase substrates.
Chen AC, Guo LY, Ostaszewski BL, Selkoe DJ, LaVoie MJ., Free PMC Article | 05/10/2010 |
| Our findings establish that APH-1a is the major mammalian APH-1 homolog present in presenilin-dependent gamma-secretase complexes during embryogenesis. | APH-1a is the principal mammalian APH-1 isoform present in gamma-secretase complexes during embryonic development.
Ma G, Li T, Price DL, Wong PC., Free PMC Article | 01/21/2010 |
| presenilin 1 (PS1)-derived fragments, mature nicastrin, APH-1, and PEN-2, associate with cholesterol-rich detergent insoluble membrane (DIM) domains of non-neuronal cells and neurons | Association of gamma-secretase with lipid rafts in post-Golgi and endosome membranes.
Vetrivel KS, Cheng H, Lin W, Sakurai T, Li T, Nukina N, Wong PC, Xu H, Thinakaran G., Free PMC Article | 01/21/2010 |
| Nct has a critical role in the stability and proper intracellular trafficking of other components of the PS1/ gamma-secretase complex but not in maintaining the association of PEN-2, APH-1, and full-length PS1 | Nicastrin is critical for stability and trafficking but not association of other presenilin/gamma-secretase components.
Zhang YW, Luo WJ, Wang H, Lin P, Vetrivel KS, Liao F, Li F, Wong PC, Farquhar MG, Thinakaran G, Xu H., Free PMC Article | 01/21/2010 |