In the August 25 Cell, researchers led by Michael Shelanski and Ottavio Arancio at Columbia University, New York, report that the enzyme UchL-1, when smuggled into neurons aboard a viral gene construct, can rescue not only synaptic deficits in brain slices treated with amyloid-β (Aβ), but also memory deficits in APP- and PS1-transgenic mice. This research draws further attention to possible dysfunction of ubiquitin-proteasome degradation in Alzheimer disease pathogenesis.

The signaling cascade the authors propose to be at play in this instance is the PKA-CREB transduction pathway that has long been implicated in basic forms of learning and memory. The study tests the working hypothesis that toxic forms or concentrations of Aβ inhibit adenylate cyclase to prevent phosphorylation of cAMP, an upstream component in this cascade. First author Bing Gong and colleagues also propose that it is UchL-1’s hydrolase activity that rescues long-term potentiation, not its alter ego as a ligase. For more detail on this study, see our original report report from this spring's Eibsee conference. —Gabrielle Strobel.

Reference:
Gong B, Cao Z, Zheng P, Vitolo OV, Liu S, Staniszewski A, Moolman D, Zhang H, Shelanski M, Arancio O. Ubiquitin Hydrolase Uch-L1 Rescues beta-Amyloid-Induced Decreases in Synaptic Function and Contextual Memory. Cell. 2006 Aug 25;126(4):775-88. Abstract

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References

News Citations

  1. Tall Science at Small Retreat: Dispatch from Germany’s Eibsee

Paper Citations

  1. . Ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory. Cell. 2006 Aug 25;126(4):775-88. PubMed.

Further Reading

Papers

  1. . Ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory. Cell. 2006 Aug 25;126(4):775-88. PubMed.

Primary Papers

  1. . Ubiquitin hydrolase Uch-L1 rescues beta-amyloid-induced decreases in synaptic function and contextual memory. Cell. 2006 Aug 25;126(4):775-88. PubMed.