Nona Semana Integrada do Instituto de Física de São Carlos

Evaluating potential inhibitors of Aβ aggregation for treatment of Alzheimer's disease

Não agendado

20m

Iniciação Científica

Palestrante

Sr. Felipe Domingues Quatroni (UFSCar)

Descrição

Alzheimer's disease (AD) is a type of dementia very common in individuals older than 65 years, characterized by memory loss and cognitive disorders. According to the ADI (Alzheimer's Disease International), in 2018 about 35 million people in the world was diagnosed with this neurodegenerative disorder (1). Several studies correlate AD with the accumulation of the β-amyloid peptide (Aβ) in the brain, which aggregate in fibrillar plaques around the neurons. Many treatments have been proposed to interrupt the synthesis of Aβ and/or to degrade them, however, recently a study showed that Aβ protects the brain against the infection of microorganisms that can pass through the blood-brain barrier (2). Treatments that only prevent the aggregation of Aβ42, represent a more adequate and less harmful alternative. In 2009, a study by Harrison et al, showed a higher amount of amyloid plaques in the brains with ascorbic acid (AA) deficiency (3), indicating that AA could have some effect on Aβ42 aggregation. In this study we investigate the role of AA on Aβ42 aggregation. Peptide samples were incubated with and without AA and analyzed at 24h intervals. Thioflavin T (ThT) fluorescence measurements were performed to quantify the amyloid fibrils by labeling β-sheet secondary structures. The ThT fluorescence analyses showed a very significant decrease in the quantity of β-sheet secondary structures for the samples incubated with AA, pointing out for an inhibitory effect of AA on the formation of amyloid fibrils. These results were confirmed by atomic force microscopy (AFM) images. Our study showed that AA inhibited the β-amyloid aggregation and, therefore, has a huge therapeutic potential for Alzheimer’s disease since the protective function of Aβ can be preserved

Referências

1 ALZHEIMER'S DISEASE INTERNATIONAL World Alzheimer Report 2018. Available at: https://www.alz.co.uk/research/WorldAlzheimerReport2018.pdf.Accessed on: January, 2019.
2 KUMAR, D.K.V. et al. Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease. Science Translational Medicine, v.8, n. 340, p. 340-372., 2016.
3 HARRISON, F.E. et al. Antioxidants and cognitive training interact to affect oxidative stress and memorry in APP/PSEN1 mice. Nutritional Neuroscience, v.12, p.203-218, 2009.doi: 10.1179/147683009X423364.