Photolytic degradation of Alzheimer's amyloid Aβ42-fibrils by sialic acid decorated glycodendrimers
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The formation of amyloid Aβ42-fibrils is linked to the pathology of cognitive dysfunction in Alzheimer's patients. There is a dire need for developing therapeutics to reverse Aβ42 fibrillation to stop or slow down the disease progression. Here, we report rationally designed sialic-acid functionalized porphyrin-cored first and second-generation dendrimers, synthesized using "click chemistry." The glycoporphyrin dendrimer showed a promising ability to degrade Aβ42 fibrils to lower-order soluble oligomers upon irradiation. The gradual fragmentation of the β-sheet-rich Aβ42 fibrils to the unstructured forms by photoactivation of the dendrimers is evident from high-resolution imaging, particle size analysis, and peptide secondary structure distribution. Further, the glycodendrimers are non-toxic even when irradiated and can rescue the neuroblastoma cells from Aβ42 fibril mediated cytotoxicity. We proposed that the photoirradiated dendrimers degrade the Aβ42 fibrils by rapturing the H-bonds by the singlet oxygen species (ROS) generated from the excited porphyrin core.
