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Human Polyclonal APH1A Primary Antibody for ELISA, WB - ABIN1001792
Periz, Fortini: Functional reconstitution of gamma-secretase through coordinated expression of presenilin, nicastrin, Aph-1, and Pen-2. in Journal of neuroscience research 2004
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Human Polyclonal APH1A Primary Antibody for IHC, ELISA - ABIN1001791
Selkoe: The cell biology of beta-amyloid precursor protein and presenilin in Alzheimer's disease. in Trends in cell biology 1999
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Human Polyclonal APH1A Primary Antibody for ChIP, ICC - ABIN261469
Gu, Chen, Sanjo, Kawarai, Hasegawa, Duthie, Li, Ruan, Luthra, Mount, Tandon, Fraser, St George-Hyslop: APH-1 interacts with mature and immature forms of presenilins and nicastrin and may play a role in maturation of presenilin.nicastrin complexes. in The Journal of biological chemistry 2003
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Human Polyclonal APH1A Primary Antibody for ELISA, WB - ABIN253299
Spasic, Raemaekers, Dillen, Declerck, Baert, Serneels, Füllekrug, Annaert: Rer1p competes with APH-1 for binding to nicastrin and regulates gamma-secretase complex assembly in the early secretory pathway. in The Journal of cell biology 2007
Using purified PSEN1 (show PSEN1 Antibodies)/Aph1A gamma-secretase and the APPC99-3XFLAG substrate, authors show that substrate shortening progressively destabilizes the consecutive enzyme-substrate complexes that characterize the sequential gamma-secretase processing of APP (show APP Antibodies); present a unifying model for how PSEN (show PSEN1 Antibodies) or APP (show APP Antibodies) mutations enhance amyloidogenic Abeta (show APP Antibodies) production, suggests that environmental factors may increase Alzheimer's Disease risk.
Data show that presenilin 1 (PS1 (show PSEN1 Antibodies))/anterior-pharynx-defective protein 1 (Aph1b), presenilin 2 (PS2 (show PSEN2 Antibodies))/Aph1aL, PS2 (show PSEN2 Antibodies)/Aph1aS and PS2 (show PSEN2 Antibodies)/anterior pharynx defective 1 homolog B (Aph1b) gamma-secretase produced amyloid beta peptide (Abeta (show APP Antibodies)) with a higher Abeta42+Abeta43-to-Abeta40 (Abeta42(43)/Abeta40) ratio than the other gamma-secretases.
Data show that presenilin 1 (PS1 (show PSEN1 Antibodies))-containing gamma-secretase complexes were targeted to the plasma membrane, whereas presenilin 2 (PS2 (show PSEN2 Antibodies))-containing ones were addressed to the trans-Golgi network, to recycling endosomes.
No statistically significant difference was detected either in APOE (show APOE Antibodies) or APH-1a polymorphisms, not suggesting a strong susceptibility to the development of Alzheimer disease.
analysis of how the conformation of presenilin, Pen-2 (show PSENEN Antibodies), Aph-1, and nicastrin (show NCSTN Antibodies) affect the function and mechanism of gamma-secretase
We demonstrate that extending the transmembrane domain of the amyloid precursor protein (show APP Antibodies)-derived C99 substrate in proximity to the cytosolic face strongly influences gamma-secretase cleavage specificity.
The -980C/G polymorphism in APH-1A promoter confers risk of Alzheimer's disease
Coexpression of wild-type or S-palmitoylation-deficient APH1aL and nicastrin (show NCSTN Antibodies) leads to marked stabilization of transgenic presenilin 1 (show PSEN1 Antibodies) in the brains of double-transgenic mice.
Endogenous Aph-1a and its proteolytic fragment have unique properties for cleavage control that may have implications for gamma-secretase regulation and intracellular distribution.
Co-overexpression of presenilin-1 (show PSEN1 Antibodies) or APH-1 abrogated gamma-secretase inhibition probably through prevention of the incorporation of CRB2 (show CRB2 Antibodies) into the gamma-secretase complex
Prostaglandin I2 accumulation in neuronal cells activates PKA/CREB (show CREB1 Antibodies) and JNK/c-Jun signaling pathways by phosphorylation, which results in APH-1alpha/1beta expression.
Thus, Leda-1/Pianp (show C12orf53 Antibodies) is constitutively processed by proprotein convertases, sheddases including MMPs and ADAM10 (show ADAM10 Antibodies)/17 and intramembrane protease gamma-secretase.
Abeta (show APP Antibodies) oligomers in the cerebrospinal fluid (CSF (show CSF2 Antibodies)) further promoted the expression of APH-1alpha/-1beta (by >2.5-fold), which enhances the gamma-cleavage of APP (show APP Antibodies) and Abeta (show APP Antibodies) deposition during AD progression
Upregulation of PS1 (show PSEN1 Antibodies)/gamma-secretase activity may be a risk factor for late onset sporadic Alzheimer's disease.
ficiency of beta-arrestin1 (show ARRB1 Antibodies) or inhibition of binding of beta-arrestin1 (show ARRB1 Antibodies) with APH-1 by small peptides reduced Abeta (show APP Antibodies) production without affecting Notch (show NOTCH1 Antibodies) processing
Pen-2 (show PSENEN Antibodies), as well as nicastrin (show NCSTN Antibodies) and Aph-1alpha, is dispensable for presenilin endoproteolysis
Aph-1 associates directly with full-length and C-terminal fragments of gamma-secretase substrates
presenilin 1 (PS1 (show PSEN1 Antibodies))-derived fragments, mature nicastrin (show NCSTN Antibodies), APH-1, and PEN-2 (show PSENEN Antibodies), associate with cholesterol-rich detergent insoluble membrane (DIM) domains of non-neuronal cells and neurons
Our findings establish that APH-1a is the major mammalian APH-1 homolog present in presenilin-dependent gamma-secretase complexes during embryogenesis.
Nct (show NCSTN Antibodies) has a critical role in the stability and proper intracellular trafficking of other components of the PS1 (show PSEN1 Antibodies)/ gamma-secretase complex but not in maintaining the association of PEN-2 (show PSENEN Antibodies), APH-1, and full-length PS1 (show PSEN1 Antibodies)
This gene encodes a component of the gamma secretase complex that cleaves integral membrane proteins such as Notch receptors and beta-amyloid precursor protein. The gamma secretase complex contains this gene product, or the paralogous anterior pharynx defective 1 homolog B (APH1B), along with the presenilin, nicastrin, and presenilin enhancer-2 proteins. The precise function of this seven-transmembrane-domain protein is unknown though it is suspected of facilitating the association of nicastrin and presenilin in the gamma secretase complex as well as interacting with substrates of the gamma secretase complex prior to their proteolytic processing. Polymorphisms in a promoter region of this gene have been associated with an increased risk for developing sporadic Alzheimer's disease. Alternative splicing results in multiple protein-coding and non-protein-coding transcript variants.
anterior pharynx defective 1 homolog A
, gamma-secretase subunit APH-1A
, presenilin-stabilization factor
, anterior pharynx defective 1a homolog
, N-acylaminoacyl-peptide hydrolase