The current study demonstrated that sarsasapogenin significantly inhibits key enzymes involved in pathogenesis of AD which are acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), BACE1 and MAO-B in a concentration dependent manner.
β-Site amyloid precursor protein cleaving enzyme 1 (BACE1) is an aspartyl protease that plays a key role in the production of amyloid β (Aβ) in the brain and has been extensively pursued as a target for the treatment of Alzheimer's disease (AD).
We found one potential candidate (referred as ligand 1) that binds to the key catalytic residues of BACE1 and predicts to inhibit abnormal APP processing and reduce Aβ levels in AD neurons.
Lanabecestat is a human β-site amyloid precursor protein-cleaving enzyme 1 inhibitor in development to slow disease progression in patients with early Alzheimer's disease.
Overall, this study suggests that PK exhibits a neuroprotective effect by inducing alternative activation of microglia and downregulating the BACE1 expression, thereby ameliorating the disease pathophysiology and reversing the cognitive decline related to Aβ deposition in AD mice.
Furthermore, the review demonstrates with increasing evidence that despite tremendous efforts and promising results conceived with BACE1 inhibitors, the latest studies suggest that their clinical use for treating Alzheimer's disease should be reconsidered.
We applied the approach to the exploration of ligands for β-site amyloid precursor protein [APP]-cleaving enzyme 1 (BACE1), a major target for Alzheimer Disease (AD), with less off-target effect toward cathepsin D. We demonstrated that the density region of BACE1 and cathepsin D ligands are well-divided, and a group of natural compounds as a target for exploration of new drug candidates also has significantly different distribution on the density map.
Herein, we highlight nine major targets associated with AD, which are acetylcholine esterase (AChE), beta-site amyloid precursor protein cleaving enzyme 1 (β-secretase, BACE-1), glycogen synthase kinase 3 beta (GSK-3β), monoamine oxidases (MAOs), metal ions in the brain, N-methyl-D-aspartate (NMDA) receptor, 5-hydroxytryptamine (5-HT) receptors, the third subtype of histamine receptor (H<sub>3</sub> receptor), and phosphodiesterases (PDEs), and their respective relationship to the disease network.
Analysis of microRNAs (miRNAs) revealed that miR-9 and miR-181a negatively coregulated BACE1 and TGFBIp, which was directly associated with the pathogenesis of AD and GCD2, respectively.
Hypomethylation of these enhancers in AD is associated with an upregulation of BACE1 transcripts and an increase in amyloid plaques, neurofibrillary tangles, and cognitive decline.
The aim of the present study was to compare the protein level of the APP secretases A-disintegrin and metalloprotease 10 (ADAM10), Beta-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PSEN1) in platelets and leukocytes from 20 non-medicated older adults with AD and 20 healthy elders, and to determine the potential use of these biomarkers to discriminate cases of AD from controls.
Thus, bergenin was screened by molecular docking study using GOLD suite (version 5.2), CCDC for predicting its activity against targets of AD management like acetylcholinesterase (AChE) (1B41), butyrylcholinesterase (BuChE) (1P0I), Tau protein kinase 1 (GSK-3β) (1J1B), BACE-1 (1FKN) wherein the GOLD score and fitness of bergenin were comparable to those of standard drugs like donepezil, galanthamine, physostigmine, etc.
Beta-secreatse (BACE-1) and cholinesterases are clinically validated targets of Alzheimer's disease (AD), for which natural products have provided immense contribution.
Transplantation of BDNF modified hUC-MSCs-derived cholinergic-like neurons significantly improved spatial learning and memory abilities in the AD rats, increased the release of acetylcholine and ChAT expression in the hippocampus, enhanced the activation of astrocytes and microglia, reduced the expression of Aβ and recombinant human beta-site APP-cleaving enzyme1 (BACE1), inhibited neuronal apoptosis, and promoted neurogenesis.
We investigated whether key biological factors such as sex, apolipoprotein E (APOE ε4) allele, and age affect longitudinal plasma BACE1 concentrations in a large monocenter cohort of individuals at risk for Alzheimer's disease.
Arylbenzofurans from the Root Bark of <i>Morus alba</i> as Triple Inhibitors of Cholinesterase, β-Site Amyloid Precursor Protein Cleaving Enzyme 1, and Glycogen Synthase Kinase-3β: Relevance to Alzheimer's Disease.