Aβ_1-42 triggers the generation of a retrograde signaling complex from sentinel mRNAs in axons.

ABSTRACT: Neurons frequently encounter neurodegenerative signals first in their periphery. For example, exposure of axons to oligomeric Aβ_1-42 is sufficient to induce changes in the neuronal cell body that ultimately lead to degeneration. Currently, it is unclear how the information about the neurodegenerative insult is transmitted to the soma. Here, we find that the translation of pre-localized but normally silenced sentinel mRNAs in axons is induced within minutes of Aβ_1-42 addition in a Ca²⁺-dependent manner. This immediate protein synthesis following Aβ_1-42 exposure generates a retrograde signaling complex including vimentin. Inhibition of the immediate protein synthesis, knock-down of axonal vimentin synthesis, or inhibition of dynein-dependent transp

SUBMITTER: Walker CA 

PROVIDER: S-EPMC6030698 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature