DJ-1 degrades transthyretin and an inactive form of DJ-1 is secreted in familial amyloidotic polyneuropathy.

DJ-1 plays roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to result in the onset of Parkinson's disease. DJ-1 has a protease-like structure and transthyretin (TTR), a protein causing familial amyloidotic polyneuropathy (FAP), was identified as a substrate for DJ-1 protease in this study. Both TTR and DJ-1 were secreted into the culture medium under normal conditions, and secreted TTR was not aggregated. Under oxidative conditions, TTR but not DJ-1 was secreted into the culture medium, resulting in aggregation. Mirror images of both the expression patterns and solubility of DJ-1 and TTR were observed in tissues of FAP patients, and an unoxidized form of DJ-1, an inactive form, was secreted into the serum of FAP patients. These results suggest that oxidative stress to cells abrogates secretion of DJ-1 and that secreted DJ-1 degrades aggregated TTR to protect against the onset of FAP.