-Secretase (BACE 1)
Design, Synthesize and Bio Evaluate 1,2 Dihydroisoquinolin 3(4H) One Derivates as Acetylcholinesterase and β Secretase Dual Inhibitors in Treatment with Alzheimer’s Disease
... With the recent research advances in molecular biology and technology, many credible hypothes- es about the progress of Alzheimer’s disease (AD) have been proposed, among which the amyloid and cholinergic hypotheses are ...
12
BACE-1 inhibition prevents the γ-secretase inhibitor evoked Aβ rise in human neuroblastoma SH-SY5Y cells
... proteases BACE-1 or g-secretase, is considered an attractive strategy for preventing dis- ease progression in patients suffering from Alzheimer ’ s ...years. BACE-1 has been a difficult ...
9
Purification and characterization of β-secretase inhibitory peptide from sea hare (Aplysia kurodai) by enzymatic hydrolysis
... The potent fraction as determined from β-secretase in- hibitory activity assay was further purified by size exclu- sion chromatography on a Sephadex G-25 gel filtration column (ø 25 × 750 mm) equilibrated with ...
8
Papillomavirus Infection Requires γ Secretase
... ously described uncoating assay (13). This assay established the procedure to monitor the exposure of the encapsidated ge- nome or an internal L2 epitope based on accessibility to antibody staining. HeLa cells were ...
10
QSAR STUDIES & DESIGNING OF POTENT HETEROCYCLIC COMPOUNDS AS γ SECRETASE INHIBITORS
... γ- secretase to release P3 or Aβ peptides, respectively. Since β-secretase and γ-secretase are responsible for the production of amyloid peptide (Aβ), which is believed to play a central role in the ...
14
Gamma secretase inhibitors of Notch signaling
... Abstract: The numerous processes involved in the etiology of breast cancer such as cell survival, metabolism, proliferation, differentiation, and angiogenesis are currently being elucidated. However, underlying ...
13
Beta-Secretase 1 (BACE1) Is Down-Regulated in Invasive Ductal Carcinoma of Breast
... of BACE, gamma-secretase, and APP levels in a larger cohort of breast cancer patients might help clarify the role of these proteins in the pathogenesis of breast ...
8
Quantification of gamma-secretase modulation differentiates inhibitor compound selectivity between two substrates Notch and amyloid precursor protein
... presenilin 1 (PS1), anterior pharynx defective-1 (Aph-1), presenilin enhancer-2 (Pen- 2), and nicastrin ...γ- secretase, as we have demonstrated that a mutation of two critical aspartate (Asp) ...
13
Pharmacological Assessment of γ Secretase Activity from Rodent and Human Brain
... The very similar γ-secretase activity and pharmacol- ogy that we observed across species with this set of compounds may be explained by the high degree of se- quence homology amongst the core protein members of ...
13
Autophagy dysfunction upregulates beta-amyloid peptides via enhancing the activity of γ-secretase complex
... Presenilin 1, Nicastrin, and Pen-2 were increased with the 3-Ma treatment (*P , ...pharynx-defective 1; aPP, amyloid protein precursor; Bace1, beta-site aPP cleavage enzyme; 3-Ma, 3-methyladenine; con, ...
9
Targeting γ-secretase in breast cancer
... used GSI from Calbiochem, Z-IL-CHO (GSI-XII), can also suppress the activity of proteasome at concentrations that show cytotoxicity in breast cancer cells (authors’ unpublished observation). Although it is unlikely that ...
8
Generation of aggregation prone N-terminally truncated amyloid β peptides by meprin β depends on the sequence specificity at the cleavage site
... though BACE-1 is clearly the most prominent enzyme responsible for the generation of Aβ1-40 and Aβ1-42 peptides from the APPwt or APPswe sequences, we propose, that meprin β may be responsible for generat- ...
16
Involvement of 5-lipoxygenase activating protein in the amyloidotic phenotype of an Alzheimer’s disease mouse model
... To this end, in the current study we chronically admi- nistered these mice with a selective and specific orally available inhibitor of FLAP activation, MK-591 [6]. At the end of the study, compared with mice receiving ...
10
Heteromers of amyloid precursor protein in cerebrospinal fluid
... In the same line, studies of sAPPα and sAPPβ levels in CSF likely would reflect potential changes in the balance between non-amyloidogenic and amyloidogenic pathways, but reports are also contradictory. Studies of sAPPα ...
11
Biological function of Presenilin and its role in AD pathogenesis
... γ-Secretase processes its substrates at γ- and ε-site, generating distinct products exemplified as Aβ and NICD. Aβ plays central role in AD pathogenesis; whereas NICD is the nuclear transcription factor activa- ...
13
Dysregulation of protein trafficking in neurodegeneration
... brain [8] and altered intracellular trafficking of BACE1 is involved in AD pathology [9-12]. A previous study sug- gested a mechanism for BACE1 elevation in AD where BACE1 is normally transported to lysosomes by GGA3, ...
9
β-site amyloid precursor protein-cleaving enzyme 1(BACE1) inhibitor treatment induces Aβ5-X peptides through alternative amyloid precursor protein cleavage
... To evaluate the biochemical effects of novel BACE1 inhibitor candidates, biomarkers that reflect target engage- ment are needed [6]. Analyzing a wide range of Aβ species in cerebrospinal fluid (CSF) gives useful ...
8
Westmeyer, Gil Gregor (2006): Identification of a BACE dimer and characterization of its biochemical and enzymatic properties. Dissertation, LMU München: Medizinische Fakultät
... of BACE at 60 kDa, the authors term this BACE species a dimer, although they do not strictly show, that this is the ...The BACE “dimer”, was not detected by a pro-domain specific antibody suggesting ...
104
Cognitive improvement of compound danshen in an Aβ25 35 peptide induced rat model of Alzheimer’s disease
... β- and γ-secretases from APP [23]. BACE1, known as a member of β-secretases, is an important enzyme that cleaved APP to produce Aβ. PS1 is one of the four core proteins in presenilin complex, which mediate the regu- ...
9
Spotlight on BACE: The secretases as targets for treatment in Alzheimer disease
... Late in 1999, β-secretase (BACE, Asp2, Memapsin) was definitively identified as a novel membrane-bound aspartic proteinase, providing the essential tool in the search for specific inhibitors of β -amyloid ...
5