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In the present study, the effect of 6-((4-fluorophenyl) selanyl)-9H-purine (FSP) was tested against memory impairment and sensitivity to nociception induced by intracerebroventricular injection of amyloid-beta peptide (Aβ) (25-35 fragment), 3 nmol/3 μl/per site in mice. Memory impairment was determined by the object recognition task (ORT) and nociception by the Von-Frey test (VFT). Aβ caused neuroinflammation with upregulation of glial fibrillary acidic protein (GFAP) (in hippocampus), nuclear factor-κB (NF-κB), and the proinflammatory cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in cerebral cortex and hippocampus. Additionally, Aβ increased oxidant levels and lipid peroxidation in cerebral cortex and hippocampus, but decreased heme oxygenase-1 (HO-1) and peroxiredoxin-1 (Prdx1) expression in the hippocampus. Anti-neuroinflammatory effects of FSP were demonstrated by a decrease in the expression of GFAP and NF-κB in the hippocampus, as well as a decrease in proinflammatory cytokines in both the hippocampus and cerebral cortex FSP protected against oxidative stress by decreasing oxidant levels and lipid peroxidation and by increasing HO-1 and Prdx1 expressions in the hippocampus of mice. Moreover, FSP prevented the activation of nuclear factor erythroid 2-related factor 2 (Nrf-2) in the hippocampus of mice induced by Aβ. In conclusion, treatment with FSP attenuated memory impairment, nociception sensitivity by decreasing oxidative stress, and neuroinflammation in a mouse model of Alzheimer's disease.

Alzheimer’s disease (AD) is the most common form of dementia in older people, and available treatments are palliative and produce undesirable side effects. The 4-phenyltellanyl-7-chloroquinoline (TQ) is an organochalcogen compound studied due to its pharmacological properties, particularly its antioxidant potential. However, TQ possesses some drawbacks such as low aqueous solubility and high toxicity, thus warranting the search for tools that improve the safety and effectiveness of new compounds. Here, we developed and investigated the biological effects of TQ-loaded polymeric nanocapsules (NCTQ) in an AD model in transgenic Caenorhabditis elegans expressing human Aβ1–42 in their body–wall muscles and Swiss mice injected with Aβ25–35. The NCTQ displayed good physicochemical properties, including nanometer size and maximum encapsulation capacity. The treatment showed low toxicity, reduced Aβ peptide-induced paralysis, and activated an endoplasmic reticulum chaperone in the C. elegans model. The Aβ injection in mice caused memory impairment, which NCTQ mitigated by improving working, long-term, and aversive memory. Additionally, no changes in biochemical markers were evidenced in mice, demonstrating that there was no hepatotoxicity in the tested doses. Altogether, these findings provide insights into the neuroprotective effects of TQ and indicate that NCTQ is a promising candidate for AD treatment.

Alzheimer's disease is a worldwide health issue, and there are currently no treatments that can stop this disease. Oxidized graphene derivatives have gained prominence in use in biological systems due to their excellent physical-chemical characteristics, biocompatibility and ability to overcome the blood-brain barrier. Other substances highlighted are those of natural origin from the Amazon biome, such as tucuma, a fruit whose oil has been widely studied in therapeutic applications. Thus, the aim of this study was to investigate the action of graphene oxide, reduced graphene oxide and tucuma oil, isolated and combined, as an alternative for treatment of Alzheimer's disease through studies in silico, in vitro, in vivo and ex vivo. Computational simulation via docking was used to verify the affinity of the substances with the proteins β-amyloid and acetylcholinesterase, in which the reduced graphene oxide was the one that showed the most favorable interaction. The results of the ab initio simulation showed that the synergism between the nanostructures and the oil occurs through physical adsorption. The experimental results revealed that the substances and their combinations were nontoxic, both at the cellular and systemic level. In general, all treatments had positive results against induced memory deficit, but reduced graphene oxide was the most prominent, as it was able to protect against memory damage in all behavioral tests performed, with anticholinesterase activity and antioxidant effect. In conclusion, the reduced graphene oxide is, among the treatments studied, the one with great therapeutic potential to be investigated in the treatment of this disease.

Alzheimer's disease (AD) is a worldwide problem, and there are currently no treatments that can stop this disease. To investigate the binding affinity of 6-((4-fluorophenyl) selanyl)-9H-purine (FSP) with acetylcholinesterase (AChE), to verify the effects of FSP in an AD model in mice and to evaluate the toxicological potential of this compound in mice. The binding affinity of FSP with AChE was investigated by molecular docking analyses. The AD model was induced by streptozotocin (STZ) in Swiss mice after FSP treatment (1 mg/kg, intragastrically (i.g.)), 1st-10th day of the experimental protocol. Anxiety was evaluated in an elevated plus maze test, and memory impairment was evaluated in the Y-maze, object recognition and step-down inhibitory avoidance tasks. The cholinergic system was investigated based on by looking at expression and activity of AChE and expression of choline acetyltransferase (ChAT). We evaluated expression and activity of Na