Oss, Groningen, December, 23rd, 2016 – Researchers from the European Research Institute for the Biology of Aging (ERIBA) University of Groningen, the Netherlands) in collaboration with the Netherlands Translational Research Center B.V. have identified an evolutionary conserved structural loop in the enzyme TDO that is critical for its function. When absent, it increases the motility and the lifespan of the roundworm Caenorhabditis elegans. The structural element was identified in a genetic screen by the group of Dr. Ellen Nollen at ERIBA. In a previous study, Nollen and colleagues showed that in C. elegans, depletion of TDO by RNA interference suppresses the toxicity from aggregation of the protein α-synuclein and extended lifespan of the worms. In humans α-synuclein aggregation has been implicated in Parkinson’s disease. In the new study they now report the remarkable finding that deletion of only three amino acids in TDO has the same effect as deletion of the whole gene. The study appeared in the online open access journal Scientific Reports, and includes 3D homology modelling studies performed at NTRC, which suggest that the three amino acid motif is involved in the binding of haem, an essential co-factor of TDO. Furthermore, the motif is conserved throughout evolution. In humans the motif is likely to be involved in the interaction with small molecule inhibitors. Such molecules are currently being developed by several companies, including NTRC, and have potential therapeutic application in Parkinson’s disease and certain cancers that express TDO.
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