Genetic reduction of the translational repressors FMRP and 4E-BP2 preserves memory in mouse models of Alzheimer’s disease

• DOI: 10.1101/2024.10.08.617315
• Publication Date: 2024-10-13T03:40:14Z
• Authors: Felipe C. Ribeiro; Danielle Cozachenco; Jean-Claude Lacaille; Karim Nader; Fernanda G. De Fe...; Mychael V. Lourenco; Argel Aguilar-Valles; Nahum Sonenberg; Sergio T. Ferreira

Abstract Alzheimer’s disease (AD) is characterized by progressive memory decline. Converging evidence indicates that hippocampal mRNA translation (protein synthesis) defective in AD. Here, we show genetic reduction of the translational repressors, Fragile X messenger ribonucleoprotein (FMRP) or eukaryotic initiation factor 4E (eIF4E)-binding protein 2 (4E-BP2), prevented attenuation synthesis and impairment induced AD-linked amyloid-β oligomers (AβOs) mice. Moreover, 4E-BP2 rescued deficits aged APPswe/PS1dE9 (APP/PS1) transgenic mouse model Our findings demonstrate strategies targeting repressors correct AD models. Results suggest modulating pathways controlling brain may confer benefits