The tau protein is considered an important qualitative and quantitative biomarker for Alzheimer’s disease in its asymptomatic phase. In 2011, biomarkers were suggested by the National Institute on Aging-Azheimer’s Association as a new criterion for the early diagnosis of Alzheimer’s disease. Thus, highlighting the non-existence of theoretical research on the subject, we investigated the binding interaction properties between phosphorylated tau protein and a theoretically modeled ligands constituted by the fullerol functionalized with radiopharmaceuticals from an in silico approach via molecular docking and density functional theory (DFT) ab initio computational simulation. The results demonstrated that the ligand with the greatest affinity-based binding energy to the protein was fullerol + F-THK5105. However, all systems were considered promising for the development of a potential diagnostic nanomarker. These theoretical results could efficiently contribute to reduce the time and the cost for future experimental preclinical studies and open new opportunities toward molecular recognition in nanomedicine.

No abstract

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.