In:
EMBO Molecular Medicine, EMBO
Abstract:
image Shared mechanisms governing both neuronal cell survival and neuroplasticity have not yet been explored therapeutically. This study demonstrates that modulation of ERK1 and KPNA2 interactions strengthens nuclear ERK signaling in the brain, promotes cognitive enhancement, and delays neurodegeneration. Genetic approaches altering ERK1 and ERK2 MAP kinase ratio, enhance global ERK signaling and attenuate neuronal cell death in vitro and in vivo . A cell penetrating peptide (RB5), designed around the unique N‐terminal domain of ERK1 MAP kinase, enhances nuclear ERK signaling in cells and in the mouse brain by mimicking ERK1 downregulation. RB5 prevents ERK1 interactions with the nuclear importin alpha KPNA2 and facilitates nuclear entry of the main Kinase ERK2. RB5 prevents synaptic dysfunction and neuronal cell death in mouse models of Huntington's, Alzheimer's and Parkinson's Disease. RB5 enhances memory formation and consolidation and facilitates synaptic plasticity in normal mice and models of neurodegeneration.
Type of Medium:
Online Resource
ISSN:
1757-4676
,
1757-4684
DOI:
10.15252/emmm.202215984
Language:
English
Publisher:
EMBO
Publication Date:
2023
detail.hit.zdb_id:
2485479-7