[Oxidative precipitation of transthyretin--a clue to elucidate amyloidosis].

Common precipitation of amyloid proteins occurs in amyloidosis such as dementia and prion diseases. The precipitates are characteristically stained with congo red, although it is not yet known why this occurs. We have found a kind of amyloid protein, transthyretin(TTR), that is S-sulfonated at the residue of cysteine in blood from patients with deficiency of molybdenum cofactor, which is essential to sulfite oxidase. The S-sulfonated TTR was easily stained with congo red, whereas TTR itself was not. Further, the S-sulfonated TTR slowly made fibrils from precipitates, which is well known as a common characteristic in amyloidosis. It seemed an important clue that S-sulfonation is as the starting reaction to induce the precipitation of the protein. We have studied reaction products from TTR and its synthetic octapeptide around the cysteine residue under moderate conditions by mass-spectrometry and estimated the reaction mechanism. Another clue is chinoform(or, clioquinol), which is effective for patients with dementia. The mechanism was assumed that metal ions such as copper and iron involved in oxidative precipitation of the proteins were masked with chinoform. In 1970, Yoshioka, one of the authors, found that in green urine from a patient with SMON disease was identified a chelate compound of chinoform with ferric ion. This finding led to the resolution of SMON disease caused by excess dose of chinoform. In this review, we discuss amyloidosis related with SMON disease.