コレスタノール代謝の栄養学と分子病理学

抄録

Cholestanol resembles cholesterol, but its significance has remained unclear because of its low concentration in the body. However, in cerebrotendinous xanthomatosis, a genetic disorder of cholesterol metabolism, deposition of cholestanol produces several pathological conditions such as tendon xanthomas, cerebellar ataxia, pyramidal signs, cataracts and dementia. We have been investigating this disease for 23 years from the viewpoint of biochemical diagnosis. We established a procedure for quantification of cholestanol by HPLC, and also an assay method for sterol 27-hydroxylase. We also found several mutations of the CYP 27 gene in 10 CTX families. Furthermore, we established experimental animals with CTX by feeding then a cholestanol diet, and produced corneal dystrophy and gallstones in mice, and apoptosis of cerebellar neuronal cells from rats. CTX can be treated with chenodeoxycholic acid, which reduces the cholestanol concentration in serum. These findings suggest that cholestanol has a toxic effect. It will be necessary to determine the cholestanol content of food for the treatment of CTX patients and to prevent the clinical manifestations produced by cholestanol administration.