نتایج جستجو برای: bace 1
تعداد نتایج: 2752751 فیلتر نتایج به سال:
Introducing mutations within the amyloid precursor protein (APP) that affect beta- and gamma-secretase cleavages results in amyloid plaque formation in vivo. However, the relationship between beta-amyloid deposition and the subcellular site of Abeta production is unknown. To determine the effect of increasing beta-secretase (BACE) activity on Abeta deposition, we generated transgenic mice overe...
Amyloid-β (Aβ) is thought to play an essential pathogenic role in Alzheimer´s disease (AD). A key enzyme involved in the generation of Aβ is the β-secretase BACE, for which powerful inhibitors have been developed and are currently in use in human clinical trials. However, although BACE inhibition can reduce cerebral Aβ levels, whether it also can ameliorate neural circuit and memory impairments...
An additional copy of the beta-amyloid precursor protein (APP) gene causes early-onset Alzheimer's disease (AD) in trisomy 21 (DS). Endosome dysfunction develops very early in DS and AD and has been implicated in the mechanism of neurodegeneration. Here, we show that morphological and functional endocytic abnormalities in fibroblasts from individuals with DS are reversed by lowering the express...
BACE, a β-secretase, is an attractive potential disease-modifying therapeutic strategy for Alzheimer's disease (AD) as it results directly in the decrease of amyloid precursor protein (APP) processing through the β-secretase pathway and a lowering of CNS amyloid-β (Aβ) levels. The interaction of the β-secretase and α-secretase pathway-mediated processing of APP in the rhesus monkey (nonhuman pr...
Amyloidogenic processing of APP by β- and γ-secretases leads to the generation of amyloid-β peptide (Aβ), and the accumulation of Aβ in senile plaques is a hallmark of Alzheimer's disease (AD). Understanding the mechanisms of APP processing is therefore paramount. Increasing evidence suggests that APP intracellular domain (AICD) interacting proteins influence APP processing. In this study, we c...
Nineteen tosylated acyl hydrazone derivatives were synthesized, and their inhibitory activities against monoamine oxidases (MAOs), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), β-secretase (BACE-1) evaluated. Compound 3o was the most potent inhibitor of MAO-A, with an IC50 value 1.54 µM, followed by 3a (IC50 = 3.35 µM). A structural comparison indicated that 3-F group in increased ...
The number of Alzheimer’s disease (AD) affected patients is increasing without any effective cure and the etiology remains to be understood. Inflammations, oxidative stress, Aβ, tauopathy are associated factors AD. Sodium butyrate (NaB) an HDAC inhibitor profoundly found neuroprotective. We have investigated neuroprotective effects NaB in SH-SY5Y cells stimulated with TNF-α/Aβ LPS-induced BV-2 ...
The Ediacaran-Cambrian transition, which incorporates the radiation of animals, lacks a robust global temporal and spatial framework, resulting in major uncertainty evolutionary dynamics this critical its relationship to changes palaeoenvironmental geochemistry. We first present new δ13Ccarb composite reference curve for Ediacaran Nama Group southern Namibia, we then outline four possible age m...
General DNA hypomethylation is associated with Alzheimer's disease (AD), but it is unclear when DNA hypomethylation starts or plays a role in AD pathology or whether DNA re-methylation would rescue early amyloid-related cognitive impairments. In an APP transgenic mouse model of AD-like amyloid pathology we found that early intraneuronal amyloid beta build-up is sufficient to unleash a global an...
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