Urea and thiourea modified polypropyleneimine dendrimers clear intracellular α-synuclein aggregates in a human cell line

Kristoffer Laumann, Ulrik Boas, Hjalte Martin Larsen, Peter M. H. Heegaard, Ann-Louise Bergström

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    Synucleinopathies are neurodegenerative pathologies in which disease progression is closely correlated to brain accumulation of insoluble α-synuclein, a small protein abundantly expressed in neural tissue. Here, two types of modified polypropyleneimine (PPI) dendrimers having either urea or methylthiourea (MTU) surface functional groups were investigated in a cellular model of synucleinopathy. Dendrimers are synthetic macromolecules that may be produced in a range of well-defined molecular sizes. Using cellomics array scan high-content screening, we show that both types of dendrimers are able to significantly reduce intracellular levels of α-synuclein aggregates dependent on the concentration, the type and molecular size of the dendrimer with the bigger size MTU-dendrimers having the highest potency. The intracellular clearance of α-synuclein aggregates by dendrimers was achieved at noncytotoxic concentrations. (Figure Presented).
    Original languageEnglish
    JournalBiomacromolecules
    Volume16
    Issue number1
    Pages (from-to)116-124
    Number of pages9
    ISSN1525-7797
    DOIs
    Publication statusPublished - 2015

    Keywords

    • Aggregates
    • Cell culture
    • Diagnosis
    • Functional groups
    • Metabolism
    • Neurodegenerative diseases
    • Urea
    • Disease progression
    • High-content screening
    • Human cell lines
    • Intracellular levels
    • Molecular size
    • Neurodegenerative
    • Surface functional groups
    • Synthetic macromolecules
    • Dendrimers

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