Alzheimer's disease (AD) is a progressive neurological disorder for which no effective cure currently exists. Research has identified β-Secretase (BACE1) as a promising therapeutic target for the mana Show more
Alzheimer's disease (AD) is a progressive neurological disorder for which no effective cure currently exists. Research has identified β-Secretase (BACE1) as a promising therapeutic target for the management of AD. BACE1 is involved in the rate-limiting step and produces toxic amyloid-beta (Aβ) peptides that lead to deposits in the form of amyloid plaques extracellularly, resulting in AD. In this connection, 60 small peptides were evaluated for their The identified hit peptides were synthesized using Solid-Phase Peptide Synthesis (SPPS), and Electrospray Ionization Mass Spectrometry (ESI-MS) elucidated their structures and 1 1 HNMR spectroscopy. According to their According to the cytotoxicity study, peptide 21 was found to be noncytotoxic at 4.64 μM, 10 μM and 20 μM. The forthcoming target of this study is to evaluate further the effect of peptide 21 in an in-vivo mice model. Show less
In the current study, we examined the antioxidant activity and anti-amyloidogenic potential of 6-aminoflavone in an adult mice model of d-galactose-induced aging. Male albino eight-week-old mice were Show more
In the current study, we examined the antioxidant activity and anti-amyloidogenic potential of 6-aminoflavone in an adult mice model of d-galactose-induced aging. Male albino eight-week-old mice were assigned into four groups: 1. the control group (saline-treated), 2. d-galactose-treated mice (100 mg/kg/day, intravenously) for eight weeks, 3. d-galactose-treated mice (100 mg/kg/day, intravenously for eight weeks) and 6-AF-treated mice (30 mg/kg/day, intravenously for the final four weeks), and 4. 6-AF-treated mice (30 mg/kg/day i.p. for four weeks). We conducted many assays for antioxidant enzymes, including lipid peroxidation, catalase, glutathione (GSH), peroxidase (POD), and sulfoxide dismutase (SOD) (LPO). Western blotting was used to assess protein expression while the Morris water maze (MWM) and Y-maze (YM) were used to study behavior. The findings show that 6-AF greatly improved neuronal synapse and memory impairment brought on by d-galactose and it significantly inhibited BACE1 to reduce the amyloidogenic pathway of A (both amyloid β production and aggregation) by upregulating Nrf2 proteins (validated through molecular docking studies) and suppressing phosphorylated JNK and TNF-α proteins in adult albino mice's brain homogenates. These findings suggest that 6-AF, through the Nrf2/p-JNK/TNF-α signaling pathway, can diminish the oxidative stress caused by d-galactose, as well as the amyloidogenic route of A formation and memory impairment. Show less