Detecting morphologically distinct oligomeric forms of alpha -synuclein.
J Biol Chem. 2009 Jan 13;
Authors: Emadi S, Kasturirangan S, Wang MS, Schulz P, Sierks MR
Neuropathologic and genetics studies, as well as transgenic animal models have provided strong evidence linking misfolding and aggregation of a synuclein to the progression of Parkinson's Disease (PD) and other related disorders. A growing body of evidence implicates various oligomeric forms of a synuclein as the toxic species responsible for neurodegeneration and neuronal cell death. While numerous different oligomeric forms of a synuclein have been identified in vitro, it is not known which forms are involved in PD, or how, when and where different forms contribute to the progression of PD. Reagents that can interact with specific aggregate forms of a synuclein would be very useful not only as tools to study how different aggregate forms affect cell function, but also as potential diagnostic and therapeutic agents for PD. Here we show that a single chain antibody fragment (syn-10H scFv) isolated from a phage display antibody library binds to a larger, later stage oligomeric form of a synuclein than a previously reported oligomeric specific scFv isolated in our lab. The scFv described here inhibits aggregation of a synuclein in vitro, blocks extracellular a synuclein induced toxicity in both undifferentiated and differentiated human neuroblastoma cell line (SH-SY5Y) and specifically recognizes naturally occurring aggregates in PD but not in healthy human brain tissue.
PMID: 19141614 [PubMed - as supplied by publisher]