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Alzheimer's Disease - Europe PMC

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Last Updated: 14 April 2022

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Design, synthesis and biological evaluation of novel N -phosphorylated and O -phosphorylated tacrine derivatives as potential drugs against Alzheimer's disease.

We obtained diamino and aminoalkylhydroxy tacrine derivatives from 9-chlorotacrine's reaction and corresponding diamines/aminoalkylalcohol derivatives. Compared to tacrine, all compounds had significantly lower AutoDock Vina scores. AChE compound 8 was the most inhibitory agent against AChE displaying IC 50 value of 6. 11 nM and a BChE 13 with an IC50 value of 1. 97 nM and were 6- and 12-fold potent than tacrine, and they were 6- and 12-fold potent than tacrine. The absence of hepatocytotoxicity in MTT assay was shown by Compound 19's lack of hepatocytotoxicity.

Source link: https://europepmc.org/article/MED/35361039


Protective effects of Forsythiae fructus and Cassiae semen water extract against memory deficits through the gut-microbiome-brain axis in an Alzheimer's disease model.

Fruits of Forsythia suspensa Vahl and Cassia obtusifolia Linne's seeds have been used to treat inflammation in Asia. Objective We investigated the mechanisms responsible for Alzheimer's disease rats' memory loss in Alzheimer's disease rats fed Forsythiae Fructus and Cassiae Semen water extracts and investigated the causes. Materials and methods Thirty Sprague-Dawley male rats received amyloid-infused hippocampal infusions, and ten rats were infused with amyloid-, a form of amyloid. The AD-FF, but not the AD-FF, measured the gut microbiota changes to be similar to the non-AD, with Bacteroidales decreasing the abundance of Bacteroidales by 32% and Lactobacillales up by 31. 8 percent and Clostridiales up by 181% and Clostridiales up by 181% during the AD-AF, but not the AD-CS. Additional clinical studies may be helpful to human AD therapy. The potential neuroprotective benefits of FF against AD may be applicable to human AD therapy.

Source link: https://europepmc.org/article/MED/35076339


Design, synthesis, and evaluation of chalcone-Vitamin E-donepezil hybrids as multi-target-directed ligands for the treatment of Alzheimer's disease.

AChE inhibitory potency was shown by the physical testing. According to me, the accumulated A 1-42 fibrils with 78. 0 and 84 percent disaggregation rate, respectively, as well as disassembled self- and Cu 2+ induced aggregation with a 78. 0 and 93. 5% percentage rate at 25 M and 93. 5% disaggregation aggregation with 78. 0 and 84. 5% disaggregation rate. In vitro, 17f had a positive neuroprotective effect on H2O 2 cell injury and showed good blood-brain barrier permeability.

Source link: https://europepmc.org/article/MED/34894968


DNA vaccines targeting amyloid-β oligomer ameliorate cognitive deficits of aged APP/PS1/tau triple-transgenic mouse models of Alzheimer's disease.

It was hypothesized that p10-MT, the A3-10 gene vaccine, has the ability to treat Alzheimer's disease. Our results showed that the p10-MT vaccine reduced A oligomer levels and plaque deposition in the cerebral cortex and hippocampus, reduced tau protein variants, reduced synaptic loss, reduced neuron loss, and improved memory function without causing any cerebral hemorrhaging.

Source link: https://europepmc.org/article/MED/35259854


Anodal transcranial direct current stimulation alleviates cognitive impairment in an APP/PS1 model of Alzheimer's disease in the preclinical stage.

In an APP/PS1 model of Alzheimer's disease in the preclinical stage, anodal transcranial direct current stimulation has been shown to reduce cognitive impairment. To measure spatial learning memory and recognition memory of mice, the Morris water maze, novel object recognition task, and novel object location test were used. The mice exposed to AtDCS sessions, six weeks after administration, had a shorter escape latency, a shorter path length, more platform area crossings, and spent more time in the target quadrant than sham-stimulated mice. The mice that were subjected to AtDCS sessions also did better in the novel object recognition and novel object location tests than sham-stimulated mice. These results show that AtDCS can improve spatial learning and memory capabilities as well as the pathological state of an APP/PS1 mouse model of Alzheimer's disease in the preclinical stage, with improvements that persist for at least six weeks.

Source link: https://europepmc.org/article/MED/35259850


Aquaporin 4 deficiency eliminates the beneficial effects of voluntary exercise in a mouse model of Alzheimer's disease.

However, it is not known if AQP4-regulated glymphatic clearance of extracellular A is involved in AD patients' positive exercise outcomes. Our findings revealed that after 2 months of voluntary wheel exercise, glial activation, perivascular AQP4 mislocalization, decreased glymphatic transport, synapse protein loss, and learning and memory defects in comparison to mice not exposed to the exercise procedure were reduced. In comparison, APP/PS1 mice that were 7 months old at the start of the trial showed impaired AQP4 polarity and reduced glymphatic clearance of extracellular A, as well as reduced glymphatic clearance, and the above-mentioned impairments were not ameliorated after the 2-month exercise intervention. AQP4 knockout mice had more significant defects in glymphatic function, A plaque deposition, and cognitive impairment, which could not be improved after the exercise intervention.

Source link: https://europepmc.org/article/MED/35142700


(D-Ser2) oxyntomodulin recovers hippocampal synaptic structure and theta rhythm in Alzheimer's disease transgenic mice.

In addition, we have shown that Oxm helps with cognitive decline and minimizes amyloid-beta deposition in Alzheimer's disease model mice. In this research, we found that Oxm intraperitoneal therapy of two weeks of intraperitoneal administration improved working memory and fear memory impairments in 9-month-old 3Tg Alzheimer's disease model mice. In addition, Oxm therapy dramatically raised the expression of synaptic-associated proteins SYP and PSD-95, as well as increased the number of dendritic spines in 3Tg Alzheimer's disease model mice. Oxm improves Alzheimer's disease transgenic mice's cognitive function by restoring hippocampal synaptic function and theta rhythm, according to these findings.

Source link: https://europepmc.org/article/MED/35142699


Abnormal characterization of dynamic functional connectivity in Alzheimer's disease.

Several studies have reported abnormal brain functional connectivity in people with Alzheimer's disease or amnestic mild cognitive impairment. In this case-control study, we used a new technique called dynamic functional connectivity to look for anomalies in patients with AD and aMCI. We established dynamic functional connectivity strength from functional magnetic resonance imaging results for each participant, and then used a support vector machine to classify AD patients and normal controls.

Source link: https://europepmc.org/article/MED/35142691


Repurposed anti-cancer epidermal growth factor receptor inhibitors: mechanisms of neuroprotective effects in Alzheimer's disease.

The improvement of cognitive and pathological sequelae in Alzheimer's disease has been shown by new studies. Despite the promising effects of epidermal growth factor receptor inhibitors in Alzheimer's disease, there is no reliable neuroprotective data in well-established animal models using epidermal growth factor receptor inhibitors due to several unexplored downstream signaling pathways. epidermal growth factor receptor inhibitors are novel therapeutic strategies that require further study in the hopes of being repositioned in Alzheimer's disease progression.

Source link: https://europepmc.org/article/MED/35142667

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions