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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 (show APH1A Antibodies)/1beta expression.
Abeta (show APP Antibodies) oligomers in the cerebrospinal fluid (CSF (show CSF2 Antibodies)) further promoted the expression of APH-1alpha (show APH1A Antibodies)/-1beta (by >2.5-fold), which enhances the gamma-cleavage of APP (show APP Antibodies) and Abeta (show APP Antibodies) deposition during AD progression
analysis of hippocampal circuitry via Aph1b-gamma-secretase/neuregulin 1 (show NRG1 Antibodies) signalling
Upregulation of PS1 (show PSEN1 Antibodies)/gamma-secretase activity may be a risk factor for late onset sporadic Alzheimer's disease.
the Aph1B/C-gamma-secretase complex is expressed in brain areas relevant to schizophrenia pathogenesis and that Aph1B/C deficiency causes pharmacological and behavioral abnormalities that can be reversed by antipsychotic drugs
study shows gamma-secretase complexes containing different Aph1 (show APH1A Antibodies) subunits have heterogeneous properties; inactivation of Aph1B gamma-secretase in an Alzheimer disease model led to improvement of disease-relevant features without Notch (show NOTCH1 Antibodies)-related side effects
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.
Expression of APH-1b increases amyloid beta peptide levels and gamma-secretase activity.
both APH-1a (show APH1A Antibodies) splice forms and APH-1b are expressed in peripheral and neuronal cells. APH (show APEH Antibodies)-1aS, APH (show APEH Antibodies)-1aL, and APH-1b form separate, proteolytically active gamma-secretase complexes containing either one of the two presenilins.
dimeric (NCSTN (show NCSTN Antibodies)/APH-1 (show APH1A Antibodies)) and trimeric (NCSTN (show NCSTN Antibodies)/APH-1 (show APH1A Antibodies)/PS1 (show PSEN1 Antibodies)) intermediates of gamma-secretase complex assembly are retained within the ER and incorporation of the fourth binding partner (PEN-2 (show PSENEN Antibodies)) also occurs on immature NCSTN (show NCSTN Antibodies) (APH-1 (show APH1A Antibodies))
knock down of APH-1a (show APH1A Antibodies), but not APH-1b, resulted in impaired maturation of nicastrin (show NCSTN Antibodies) and reduced expression of presenilin 1 (show PSEN1 Antibodies), presenilin 2 (show PSEN2 Antibodies), and PEN-2 (show PSENEN Antibodies) proteins
APH-1b variant protein is destabilized, and the fourth transmembrane domain plays an important role in the protein stability and function of APH-1 (show APH1A Antibodies).
These results collectively indicate that the three forms of APH-1 (show APH1A Antibodies) can replace each other in presenilin (PS) complexes and that the transmembrane GxxxG region is essential for the stability of the APH-1 (show APH1A Antibodies) protein as well as the assembly of PS complexes.
These data suggest that a cooperative mechanism involving APOE (show APOE Antibodies) and APH-1b plays a role in the susceptibility to develop AD.
A non-synonymous SNP in the gamma-secretase component APH1B (Phe217Leu; rs1047552)is significantly associated with premature coronary atherosclerosis in Dutch males.
This gene encodes a multi-pass transmembrane protein that is a functional component of the gamma-secretase complex, which also contains presenilin and nicastrin. This protein represents a stabilizing cofactor for the presenilin holoprotein in the complex. The gamma-secretase complex catalyzes the cleavage of integral proteins such as notch receptors and beta-amyloid precursor protein.
anterior pharynx defective 1c homolog
, gamma-secretase subunit APH-1B
, anterior pharynx defective 1b homolog
, APH1B homolog
, anterior pharynx defective 1b
, putative gamma-secretase subunit APH-1C
, anterior pharynx defective 1 homolog B