Researchers have been able to use a common chaperone protein, Hsp70, to reverse the loss of function in the nerves of mice with diabetes.
Writing in ASN NEURO, Michael J. Urban and colleagues at the University of Kansas suggest that Hsp70 could be used in the future to cure the loss of feeling in the limbs that afflicts many diabetics.
Diabetic peripheral neuropathy (DPN) is a common complication of diabetes and leads to high levels of pain, the death of sensory neurons and numbness in the extremities. Caused by increased blood glucose levels leading to vasoconstriction, neuronal hypoxia and detrimental glycosylation of key proteins, it has been a difficult condition to cure, with treatments limited to heavy glucose control and pain management.
However, this new study, based around the up regulation of Hsp70 by inhibiting the activity of Hsp70's regulatory protein, Hsp90, has led to the reversal of neuronal degeneration in mice with DPN. Hsp90, a key regulator of Hsp70 and the cellular heat shock response (HSR), had its activity inhibited by a novel C-terminal inhibitor, KU-32. The resultant increase in Hsp70 activity is believed to reverse DPN by Hsp70's ability to refold aggregated and damaged proteins, whilst Hsp70 provides pain relief by its ability to block the JNK protein kinase activity.
- Michael Urban, Chengyuan Li, Cuijuan Yu, Yuanming Lu, Joanna Krise, Michelle McIntosh, Roger Rajewski, Brian Blagg, Rick Dobrowsky. Inhibiting heat shock protein 90 reverses sensory hypoalgesia in diabetic mice. ASN NEURO, 2010; DOI: 10.1042/AN20100015
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