Scientists at Hokkaido University to Analyze Parkinson's and Alzheimer's Disease Pathways using HuCAL-based Antibodies

 

04 December 2006

AbD Serotec, a division of MorphoSys AG, Munich, announced today the publication of a scientific research paper that was researched using antibodies generated from the MorphoSys HuCAL GOLD antibody library. Using the rapid, high-throughput antibody generation system, a set of monoclonal and fully human mini-antibodies was selected that specifically recognize an oxidized form of the DJ-1 (PARK7) protein. Scientists working a team with Dr. Hiroyoshi Ariga at Japan's renowned Hokkaido University subsequently analyzed these antibodies in detail and published the results in the Neuroscience Letters journal. The analysis demonstrates that the HuCAL-based antibody fragments provide a set of useful probes for studying the DJ-1 protein, specifically oxidized at a single amino acid. DJ-1 was initially identified by researchers at Hokkaido University as a novel cancer target and has recently been linked to certain forms of Parkinson's and Alzheimer's disease. AbD Serotec will make the DJ-1 specific antibody available via its sales catalog and customer website.

DJ-1 is considered to play a role in transcriptional regulation and anti-oxidative stress reaction, and loss of its function is thought to result in the onset of Parkinson's disease. The protein has three potential oxidation sites - cysteines at amino acid numbers 53, 46 and 106. Recent findings indicate that the oxidation status, especially at position C106, modulates functions of DJ-1, and deregulation of C106 oxidation leads to the onset of diseases. Beyond its potential involvement in Parkinson's and Alzheimer's disease, it has been reported that expression levels of DJ-1 were elevated in patients with breast, smoking-derived lung, prostate and melanoma cancers and that DJ-1 was secreted into the serum in patients with breast and melanoma cancers. Additionally, secretion of DJ-1 into the blood plasma of patients with ischemia-derived stroke has also been reported.

Oxidized C106-specific DJ-1 antibodies have been selected from the HuCAL GOLD library by using a DJ-1 derived peptide containing the crucial oxidized cysteine 106. By blocking the antibody library with non-oxidized peptide, the antibody selection process was driven towards the right epitope. Simultaneously, the use of different peptide-carrier proteins in subsequent selection rounds prevented selection of carrier-specific antibodies. As a result, the majority of antibodies obtained showed specificity to the oxidized form of the DJ-1.

"C106-oxidized DJ-1 specific antibodies, which we could not obtain using animal-based immunization methods, should be useful for diagnosis of several DJ-1 related diseases, including neurodegenerative disorders and cancer", commented Dr. Hiroyoshi Ariga, Hokkaido University.

"AbD Serotec is very pleased that Dr. Ariga's team has chosen our HuCAL antibody generation service for their research on this multifaceted target", commented Dr. Achim Knappik, senior director of R&D at AbD Serotec. "The results underpin the potential of the HuCAL GOLD recombinant antibody technology to generate highly-specific antibodies by guided selection that can distinguish between closely related antigens."

To view an abstract of the Neurosciences Letter paper 'Establishment of specific antibodies that recognize C106-oxidized DJ-1' please visit www.sciencedirect.com.


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