Abnormal (misfolded) form of human prion protein displays high propensity towards self-association which may result in formation of insoluble fibrillar
The misfolding and aggregation of the amyloid-b (Ab) peptide plays a central role in the pathogenesis of Alzheimer's disease (AD). Targeting the generation or structure of the highly cytotoxic oligomeric species that form during the deposition process represents a promising therapeutic strategy to reduce the toxicity associated with Ab aggregation. Through an integrative approach combining in vitro techniques, including chemical kinetics, atomic force microscopy, and other biophysical measurements, with in vivo methods, including neuroblastoma cells and a C. elegans model of neurodegenerative disease, we have investigated modes by which oligomeric aggregates can be targeted with small molecules. We thus report compounds that show that the cytotoxicity related to Ab aggregation can be reduced both by the promotion of fibril formation and by the direct modification of oligomer structure. Indeed, both approaches were revealed to generate aggregates with unique tinctorial properties and reduced cytotoxicity. These results provide insight into the role of oligomers in the induction of cellular toxicity, and suggest that novel mechanisms of modulating the aggregation process, in addition to inhibiting oligomer production, may provide a viable therapeutic route for the treatment of AD.
OBJECTIVES: To describe the main impacts of physical inactivity, increased screen time, and violence against children on the psychological and cognitive development supported by changes in habits during the COVID-19 pandemic. METHODS: A narrative review of the literature with publications from 2012 to 2021 was conducted based on data from the U.S. National Library of Medicine (PubMed) and from the Scientific Electronic Library Online (SciELO). The following keywords were used: “Child Behavior”; “Screen time”; “Covid-19”; “Sedentary behavior” e “Domestic Violence”. RESULTS: An intensification of the use of electronic devices, increased rates of child abuse and children’s physical inactivity during the COVID-19 pandemic was observed. CONCLUSION: Social isolation due to the COVID-19 pandemic resulted in the aggravation of pre-existing problems in children, such as increased screen time, physical inactivity and violence against children.
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