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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Lithium and antidepressants: potential agents for the treatment of Rett syndrome.

Rett syndrome (RTT) is a severe neurodevelopmental disorder occurring almost exclusively in females. It is caused by mutations in gene encoding methyl-CpG-binding protein 2 (MECP2) in the majority of cases. MECP2 was originally thought to be a global transcriptional repressor, but recent evidence from studies of animals suggests that it may have a role in regulating neuronal activity-dependent expression of specific genes such as Bdnf. A recent report demonstrated that deletion of Bdnf in Mecp2 mutants caused earlier onset/accelerated disease progression, whereas BDNF overexpression in the Mecp2 mutant brain led to later onset/slower disease progression, suggesting that manipulation of BDNF expression/signaling in the brain could be therapeutic for this disease. Lithium and antidepressants have been demonstrated to increase central BDNF levels or signaling in human as well as animal studies. Thus, it is proposed that these agents could have therapeutic potential for RTT subjects. Several points regarding the use of these agents in RTT are discussed. Further evaluation of the therapeutic effects of these drugs in RTT animal models is needed before clinical trials can begin.[1]


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