Long-term memory, namely the capacity of storing information for a long period of time, depends on protein synthesis. This event is triggered by eIF2α (eukaryotic translation initiation factor 2α). When present in its unphosphorylated state, this protein initiates the translation of RNA into proteins. Conversely, eIF2α becomes inactive when phosphorylated. In this condition, protein synthesis is blocked and the long-term memory impaired.
Carmela Sidrauski, University of California, USA, and colleagues discovered ISRIB (pictured), a molecule which renders the cells insensitive to eIF2α phosphorylation. The new compound, a symmetric bis-glycolamide with a central bi-substituted cyclohexane, increased protein synthesis and improved long term memory when administered to rodents. Moreover, it showed good pharmacokinetic properties and it did not elicit toxic effects.
ISRIB might, therefore, constitute a useful treatment for diseases associated to memory impairment.
- Pharmacological brake-release of mRNA translation enhances cognitive memory
C. Sidrauski, D. Acosta-Alvear, A. Khoutorsky, P. Vedantham, B. R. Hearn, H. Li, K. Gamache, C. M. Gallagher, K. K.-H. Ang, C. Wilson, V. Okreglak, A. Ashkenazi, B. Hann, K. Nader, M. R. Arkin, A. R. Renslo, N. Sonenberg, P. Walter
eLife 2013, 2, e00498–e00498.