Increased levels of 4HNE-protein plasma adducts in Rett syndrome.

OBJECTIVE

Rett syndrome (RTT) is a neurological disorder and a leading cause of mental retardation in females. It is caused by mutations in methyl-CpG-binding protein 2 (MeCP2) gene and more rarely in cyclin-dependent kinase-like 5 (CDKL5) and forkhead box protein G1 (FOXG1) genes. Increased oxidative stress (OS) has been documented in MeCP2-RTT patients. Here, we evaluated the levels of 4-hydroxynonenal plasma protein adducts (4HNE-PAs) in MeCP2-, CDKL5-, and FOXG1-RTT and in their clinical variants.

DESIGN AND

METHODS

4HNE-PAs were determined by Western blot in plasma from healthy subjects and RTT patients.

RESULTS

4HNE-PAs levels were increased in MeCP2- and CDKL5-related RTT but not in FOXG1-related RTT.

CONCLUSION

These results showed that OS is present in RTT clinical variants and could play a key role in RTT pathogenesis. Under the OS point of view FOXG1-related RTT appears to be distinct from the MeCP2/CDKL5, suggesting a distinct mechanism involved in its pathogenesis.