Development and Application of Single Chain Antibodies for PD Therapy
Abstract
In PD the insult to the dopamine (DA) neuron is posited to involve oxidative injury mediated by mitochondrial respiratory abnormalities and through participation of oxidative adducts made onto DA and presynaptic target proteins such as a-synuclein. The misfolding of a-synuclein engendered by oxidative adduct formation is hypothesized to be a critical participating process in Lewy Body formation and dopamine neuron compromise and death. Our central hypothesis purports that protein aggregates forming within dopaminergic neurons are seeded and require misfolded a-synuclein and that these aggregates are cytotoxic thereby contributing directly to neuron death. Thus targeting a-synuclein protein misfolding will enable the development of effective therapy. The main goal of this application is to identify and characterize humanized single chain antibodies (scFvs) that recognize structural epitopes on a-synuclein misfolding. Thus far, we have expressed and purified wildtype and a-synuclein; generated altered conformers of these proteins; screened for and identified synuclein-specific scFvs. Finally, we have begun the characterization of these synuclein-specific scFvs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2003
- Accession Number
- ADA421276
Entities
People
- Howard J. Federoff
Organizations
- University of Rochester