title: Urea and thiourea modified polypropyleneimine dendrimers clear intracellular α-synuclein aggregates in a human cell line.
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.
authors.affiliation: Innate Immunology Group, National Veterinary Institute, Technical University of Denmark , 1870 Frederiksberg C, Denmark.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Laumann
authors.forename: Ulrik
authors.initials: U
authors.lastname: Boas
authors.forename: Hjalte M
authors.initials: HM
authors.lastname: Larsen
authors.forename: Peter M H
authors.initials: PM
authors.lastname: Heegaard
authors.forename: Ann-Louise
authors.initials: AL
authors.lastname: Bergström
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D011126:Polypropylenes / Q000737:chemistry / Q000378:metabolism*; D013890:Thiourea / Q000737:chemistry / Q000378:metabolism*; D014508:Urea / Q000737:chemistry / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D050091:Dendrimers; D011126:Polypropylenes; D051844:alpha-Synuclein; C443641:poly(propyleneimine); D014508:Urea; D013890:Thiourea