CloneID: D5 (D5E)
Heavy Chain modification: Fc Silent™
Antigen Long Description: The original antibody was isolated from a human Tomlinson I and J scFv antibody libraries by panning the library against oligomeric α-synuclein immobilized on a mica surface. The presence of positive binding phage after each round was verified by incubating an aliquot of eluted phage with α-synuclein and imaging by Atomic Force Microscopy (AFM).
Buffer Composition: PBS with 0.02% Proclin 300.
Chimeric Use Statement: This is a reformatted mouse IgG2b Fc Silent™ antibody, based on the original mouse scFv format, created for improved compatibility with existing reagents, assays and techniques.
Available Custom Conjugation Options: AP, HRP, Fluorescein, APC, PE, Biotin Type A, Biotin Type B, Streptavidin, FluoroProbes 647H, Atto488, APC/Cy7, PE/Cy7
Uniprot Accession No.: P37840
Specificity Statement: This antibody recognizes the early-stage oligomeric morphological form of human alpha-synuclein. Alpha-synuclein is a small 140 amino acid presynaptic neuronal protein, a major component of Lewy bodies and a member of the synuclein family. Misfolding, abnormal accumulation, and secretion of α-Synuclein (α-Syn) are closely associated with synucleinopathies, including Parkinson’s disease (PD). α-syn is abundant in the brain, and smaller amounts are found in the heart, muscles, and other tissues. In the brain, α-syn is found mainly at the tips of neurons in the specialized structures known as presynaptic terminals and has been shown to comprise up to ∼1% of total proteins in the neuronal cytosol. Recent evidence suggests that α-synuclein (α-syn) can contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS).
Application Notes (Clone): The binding of this antibody to oligomeric forms of alpha-synuclein was confirmed using ELISA. This antibody is not capable of recognizing monomeric and fibrillar forms of alpha-synuclein. This antibody could also recognize molecular masses of about 29 and 56 kDa corresponding to dimeric and tetrameric forms of alpha-syn form in a western blot (PMID: 17391701; 19141614). The scFv form of this antibody binds only to an oligomeric form of α-synuclein and inhibits both aggregation and toxicity of α-synuclein in vitro (PMID: 17391701). This antibody could recognize the early stage alpha-synuclein aggregates occurring during (4–10 day) time points (PMID: 19141614). Intracellular expression of scFv version of this antibody containing a non-conventional secretion signal sequence could successfully bind their cytosolic targets and secrete them from a mammalian cell. It was further demonstrated that secretion of scFv bound oligomeric alpha-syn aggregates provides complete protection from a-syn-induced toxicity (PMID: 19394405). A fusion protein comprising D5 scFv, cell penetrating peptide like penetratin were found to be effective in Lewy body disease. It specifically targeted α-syn oligomers and reduced the accumulation of α-syn and ameliorated functional deficits when delivered late in disease development (PMID: 27606342).