signature=c54f775d9c1f2b656d690e4046869d39,Altered levels of high-energy phosphate compoundsin fibro...

摘要：

The pathogenesis of neurodegeneration in neuronal ceroid lipofuscinosis (NCL) is still not clear despite progress in mutation analysis of these diseases. We have recently observed anomalies at the level of the mitochondria) ATPsynthase (complex V of the respiratory chain) in fibroblasts from children with CLN1, CLN2, CLN3 and in an ovine model (OCI-6). The measurements were carried out in vitro. If these alterations were of relevance in vivo as well, contents of high-energy phosphate compounds should be reduced. In the present study, we measured levels of creative phosphate (CP), ATP, ADP and AMP in fibroblasts from children with CLN1, CLN2, CLN3 and in OCL6. ATP was reduced to about 50% of normal in CLN1, CLN2 and CLN3, ADP was about 30% of normal in these cells, and CP was 50% of normal in CLN1 and CLN2 but remained normal in CLN3. In fibroblasts of NCL-sheep, however, CP and ADP were increased to 690% and 220% of normal, respectively, while ATP remained normal. If the anomalies found in cellular energy metabolism in fibroblasts were expressed in neurons from NCL patients andNCL sheep 'slow-onset excitotoxicity' could occur leading to cellular dysfunction and eventually to cell death.

展开