Two Glycoconjugates of Dopamine, IPX-750 and IPX-760, Attenuate α-Synuclein Oligomerization

Academic Article

Abstract

  • Alpha-synuclein (α-synuclein) is a small protein that is expressed in neurons in the substantia nigra. Its function in the healthy brain is currently unknown, but has been found to be the major constituent of Lewy bodies, protein aggregations that are a hallmark of Parkinson's disease. The effect of IPX-750 or IPX-760, two glycoconjugates of dopamine, on α-synuclein aggregation was tested in a cell base assay Tet-off cell line consisting of neurons co-expressing α-synuclein proteins conjugated to the amino terminal (α-synuclein-nGL) or the carboxyl region (α-synuclein-cGL) of the Gaussia luciferase protein. Aggregation of two α-synuclein proteins brings the two regions of Gaussia luciferase together which results in increased fluorescence that is captured by a microplate reader. The effect of each drug on α-synuclein aggregation was tested by growing cells for 24hrs in the absence of tetracycline to allow the expression of α-synuclein-nGL and α-synuclein-cGL. Cells were treated with IPX-750 or IPX-760 at 0.01, 0.05, and 0.1µM followed by fluorescence assay at 24hrs. The effect of each treatment was compared between treated and non-treated samples and expressed as % aggregation reduction. Our results showed that IPX-750 reduced α-synuclein aggregation by 5, 15 and 16%, respectively, while IPX-760 reduced α-synuclein aggregation by 18, 17, and 18%, respectively. These results demonstrate that IPX-750 and 760 are potential candidates for Parkinson disease treatment.
  • Published In

  • J Nanomed Nanosci  Journal
  • Keywords

  • Alpha Synuclein, Dopamine, IPX-750, IPX-760, Lewy Bodies, Parkinson’s Disease
  • Author List

  • Avery DV; Harrelson A; Xavier N; Patel KV; Huang YE; Garner J; Nugent K; Unlap MT; Suleiman Z; Avery DV