Proceedings of the Japan Academy, Ser. B, Physical and Biological Sciences
The Proceedings of the Japan Academy, Series B was founded in 1912 as the Proceedings of the Imperial Academy by the then Imperial Academy of Japan (now the Japan Academy). The Journal was split to the Proceedings of the Japan Academy, Series A and Series B in 1977. PJA Series B publishes both reviews and original articles in broad fields of natural sciences, such as chemistry, physics, astronomy, earth sciences, biology, engineering, agricultural sciences and medical sciences. Ten issues are published per year. The entire content is now freely available online through J-STAGE. Its original aim was to publish important scientific achievements emanating from Japan, but it now welcomes contributions internationally from any parts of the world.
Vol. 88 No. 1 (2012)
Reviews
Peculiarity of methoxy group-substituted phenylhydrazones in Fischer indole synthesis
Yasuoki MURAKAMI
Yasuoki MURAKAMI
Proc. Jpn. Acad., Ser. B, Vol. 88, 1-17 (2012) [abstract] [PDF]
Pharmacological chaperone therapy for Fabry disease
Satoshi ISHII
Satoshi ISHII
Proc. Jpn. Acad., Ser. B, Vol. 88, 18-30 (2012) [abstract] [PDF]
Cover Illustration
Pharmacological chaperone facilitates the correct folding of mutant enzyme
A newly synthesized α-galactosidase A (α-Gal A) is extruded into the lumen of the endoplasmic reticulum (ER) according to its ER signal peptide as well as other lysosomal enzymes and the secreted proteins. In the ER, most proteins are retained until they are correctly folded and assembled. Wild-type α-Gal A is folded correctly in a short time, and it leaves the ER and reaches the final destination lysosomes. In contrast, a single amino acid substitution detected in the patient with Fabry disease causes a high frequency of misfolding and retained in the ER. Prolonged retention of misfolded proteins in the ER leads to their degradation.
Dr. Ishii et al. discovered the technology to facilitate the correct folding of mutant enzyme by using pharmacological chaperone 1-deoxygalactonojirimycin (DGJ). The frequency of correct folding of mutant α-Gal A was increased by the binding of DGJ at an active site of the enzyme. The mutant α-Gal A with DGJ was normally transported out of the ER and reached the lysosomes. Clinical trials of this technology for Fabry disease are being conducted. The concept of this technology may be broadly applicable to other inherited diseases.
Dr. Ishii et al. discovered the technology to facilitate the correct folding of mutant enzyme by using pharmacological chaperone 1-deoxygalactonojirimycin (DGJ). The frequency of correct folding of mutant α-Gal A was increased by the binding of DGJ at an active site of the enzyme. The mutant α-Gal A with DGJ was normally transported out of the ER and reached the lysosomes. Clinical trials of this technology for Fabry disease are being conducted. The concept of this technology may be broadly applicable to other inherited diseases.
Hiroki Maruyama
Specially Appointed Professor
Department of Clinical Nephroscience,
Niigata University Graduate School of Medical and Dental Sciences
Specially Appointed Professor
Department of Clinical Nephroscience,
Niigata University Graduate School of Medical and Dental Sciences
