A protein pair best known for their role in bone remodelling may have an unexpected role in the brain, helping to control fever and female body temperature, a Nature paper suggests.
The proteins, RANKL and RANK, are expressed in a particular type of brain cell called an astrocyte, Josef Penninger and colleagues show. Mice and rats injected with RANKL develop severe fever, whereas genetically engineered mice with astrocytes lacking RANK appear fever-resistant. The finding tallies with clinical data from two children carrying RANK mutations who failed to develop fever during pneumonia. Female mice lacking RANK also have an increased body temperature, the team show, suggesting that RANKL/RANK help control temperature in a gender-specific manner.
Antibodies against RANKL are in development at present for the treatment of various metabolic bone diseases such as osteoporosis. The authors speculate that the hot flushes that often accompany osteoporosis and hormonal changes in older women could be explained by the actions of RANKL/RANK.
Josef Penninger (Institute for Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria)
(C) Nature press release.
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