Objective: To investigate whether short interfering RNAs(siRNAs) of beta-site APP cleaving enzyme (BACE) can inhibit the expression of BACE in mammalian cells.
Methods: The gene of EGFP, U6 promoter and beta-secretase targeting siRNA were cloned by PCR, respectively. The PCR products were inserted into plasmid pLXSN. The interfering vector pLXSN/EGFP-U6-siBACE was transferred into SK-N-SH cells to express BACE. The inhibition effect of BACE siRNA on BACE expression was investigated by fluoroscopy and immunohistochemistry method.
Result: The interfering vector pLXSN/EGFP-U6-siBACE was constructed successfully. The BACE siRNA inhibited the expression of BACE in the SK-N-SH cells specifically and effectively, and the production of A beta was reduced.
Conclusion: BACE siRNA can inhibit the expression of BACE gene of mammalian cells.
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http://dx.doi.org/10.3785/j.issn.1008-9292.2006.06.009 | DOI Listing |
Curr Pharm Des
January 2025
Department of Translational Medicine and for Romagna, University of Ferrara, Via Luigi Borsari 46, 44121, Ferrara, Italy.
Amyloid beta (Aβ) dyshomeostasis is considered the main biological aberration in Alzheimer's Disease (AD) pathology. The interplay between Aβ formation and clearance is predominantly modulated by a disintegrin and a metalloproteinase 10 (ADAM10, α-secretase) and β-site APP Cleaving Enzyme 1 (BACE1), the two pivotal enzymes in both non-amyloidogenic/amyloidogenic and amyloidolytic pathways. Emerging evidence suggests that aberrations in ADAM10 and BACE1 expression, activity, and function in the brain of AD patients also manifest in peripheral fluids, suggesting their potential as blood-based biomarkers for AD diagnosis.
View Article and Find Full Text PDFMetabol Open
December 2024
Department of Physiology, University of Medical Sciences, Ondo City, Nigeria.
Diabetes mellitus, a chronic metabolic disorder, has significant global health implications, particularly due to its neurological complications, such as diabetic neuropathy. This condition increases the risk of neurodegenerative diseases by affecting peripheral nerves and cognition. , known for its neuroprotective properties, shows promise as a therapeutic option for addressing these complications.
View Article and Find Full Text PDFAddict Biol
December 2024
Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, California, USA.
The early initiation of binge-drinking and biological sex are critical risk factors for the development of affective disturbances and cognitive decline, as well as neurodegenerative diseases including Alzheimer's disease. Further, a history of excessive alcohol consumption alters normal age-related changes in the pattern of protein expression in the brain, which may relate to an acceleration of cognitive decline. Here, we aimed to disentangle the interrelation between a history of binge-drinking during adolescence, biological sex and normal aging on the manifestation of negative affect, cognitive decline and associated biochemical pathology.
View Article and Find Full Text PDFMol Neurodegener
November 2024
Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT, 06030-3401, USA.
Background: The accumulation of β-amyloid (Aβ) peptides into insoluble plaques is an early pathological feature of Alzheimer's disease (AD). BACE1 is the sole β-secretase for Aβ generation, making it an attractive therapeutic target for AD therapy. While BACE1 inhibitors have been shown to reduce Aβ levels in people with AD, clinical trials targeting BACE1 have failed due to unwanted synaptic deficits.
View Article and Find Full Text PDFPhytother Res
November 2024
Institute of Biomolecular Chemistry (ICB), National Research Council (CNR), Pozzuoli (NA), Italy.
Cannabidiolic (CBDA) and cannabigerolic (CBGA) acids are naturally occurring compounds from Cannabis sativa plant, previously identified by us as dual PPARα/γ agonists. Since the development of multitarget-directed ligands (MTDL) represents a valuable strategy to alleviate and slow down the progression of multifactorial diseases, we evaluated the potential ability of CBDA and CBGA to also inhibit enzymes involved in the modulation of the cholinergic tone and/or β-amyloid production. A multidisciplinary approach based on computational and biochemical studies was pursued on selected enzymes, followed by behavioral and electrophysiological experiments in an AD mouse model.
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