Emerging novel concept of chaperone therapies for protein misfolding diseases

作者：Suzuki Yoshiyuki^*

来源：Proceedings of the Japan Academy Series B-Physical and Biological Sciences, 2014, 90(5): 145-162.

DOI：10.2183/pjab.90.145

• chaperone therapy
• inhibitory chaperone
• non-inhibitory chaperone
• molecular chaperone
• protein misfolding
• lysosomal disease

Chaperone therapy is a newly developed molecular therapeutic approach to protein misfolding diseases. Among them we found unstable mutant enzyme proteins in a few lysosomal diseases, resulting in rapid intracellular degradation and loss of function. Active-site binding low molecular competitive inhibitors (chemical chaperones) paradoxically stabilized and enhanced the enzyme activity in somatic cells by correction of the misfolding of enzyme protein. They reached the brain through the blood-brain barrier after oral administration, and corrected pathophysiology of the disease. In addition to these inhibitory chaperones, non-competitive chaperones without inhibitory bioactivity are being developed. Furthermore molecular chaperone therapy utilizing the heat shock protein and other chaperone proteins induced by small molecules has been experimentally tried to handle abnormally accumulated proteins as a new approach particularly to neurodegenerative diseases. These three types of chaperones are promising candidates for various types of diseases, genetic or non-genetic, and neurological or non-neurological, in addition to lysosomal diseases.

• 出版日期2014-5
• 单位河北医科大学