A lack of good animal models had prevented scientists from exploring the effects of Trk receptor abnormalities on neuronal cell death, wrote Tessarollo and colleagues. However, they wrote, their trisomic mouse strain has enabled such studies, with surprising results.
"The cause of the accelerated cell death has the potential to be multigenic, since hundreds of genes are dysregulated in trisomies," they wrote. "Surprisingly, we have found that an alteration in TrkB receptor signaling is sufficient for the development of this phenotype, suggesting that dysregulation of a single gene is sufficient to cause cellular alterations resulting in neuron death."
In a preview of the two papers, Eero Castrn and Heikki Tanila of the University of Helsinki wrote in the same issue of Neuron "Although the results of these studies are still far from suggesting any new therapeutic strategies for Down's syndrome, it might be possible that drugs influencing APP processing could in the future help to restore the retrograde transport of NGF and thereby cognitive symptoms in Down's syndrome. In any case, the papers provide interesting insights into the pathophysiology of Down's syndrome and underline the notion that the primary aim of treatment of neurodegenerative disorders is not to keep neurons alive but to keep them connected."
(Salehi et al.)
The researchers include Ahmad Salehi, Pavel V. Belichenko, Ke Zhan, Chengbiao Wu, Janice S. Valletta, Ryoko Takimoto-Kimura, Alexander M. Kleschevnikov and William C. Mobley of Stanford University in Stanford, CA; Jean-Dominique Delcroix of Stanford University in Stanford, CA and the European Brain Research Institute, Rita Levi-Montalcini Foundation in Rom
Contact: Heidi Hardman