Cat. No.
MABL-390
Application
functional assay, therapeutic
Isotype
Engineer antibody
Species Reactivity
Human
Clone No.
VH14 (NAC14)
From
Recombinant Antibody
Specificity
This antibody binds the hydrophobic non-amyloid component (NAC) of α-synuclein between amino acids 53-87. More specifically, this antibody showed high binding to linear epitope comprising aa 61-78 of alpha-syn. 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 cytosol. Recent evidence suggests that α-synuclein (α-syn) can contribute to the pathogenesis of amyotrophic lateral sclerosis (ALS).
Alternative Names
SNCA; NACP; PARK1; alpha-syn; α-Synuclein; α-syn; Non-A beta component of AD amyloid; Non-A4 component of amyloid precursor
UniProt
P37840
Immunogen
The original antibody was isolated from a naïve repertoire of human scFv antibodies using yeast surface display to select binders against NAC peptide of human alpha-synuclein.
Application Notes
The fusion of a proteasome-targeting PEST motif to this intrabody enhanced the solubility of the nanobody in cytoplasm and significantly enhanced degradation of the target protein, α-syn-GFP (PMID: 22929188). The in vivo therapeutic potential of gene therapy for delivery of proteasomedirected nanobodies selectively targeting α-syn was evaluated in a synuclein overexpression-based PD model. Post-mortem assessments of the substantia nigra (SN) of Sprague–Dawley rats after intracellular delivery of VH14-PEST showed that it markedly reduced the level of phosphorylated Serine-129 α-syn labeling relative to saline-treated animals (PMID: 30155513). A bifunctional antibody generated by fusing VH14 to a proteosome-targeting signal was able to counteract heterologous proteostatic effects of mutant α-Syn on mutant huntingtin Exon1 and protect against α-Syn toxicity using propidium iodide or Annexin V readouts (PMID: 27824888).
Antibody First Published
Lynch et al. An ScFv Intrabody Against the Non-Amyloid Component of Alpha Synuclein Reduces Intracellular Aggregation and Toxicity. J Mol Biol. 2008 Mar 14; 377(1): 136–147.PMID:18237741
Note on publication
Describes the generation of a yeast surface display library of an entire naïve repertoire of human scFv antibodies to select binders against NAC peptide of human alpha-synuclein.
Size
100 μg Purified antibody.
Concentration
1 mg/ml.
Purification
Protein A affinity purified
Buffer
PBS with 0.02% Proclin 300.
Storage Recommendation
Store at 4⁰C for up to 3 months. For longer storage, aliquot and store at - 20⁰C.
