Relevance of ERK1/2 Post-retrieval Participation on Memory Processes: Insights in Their Particular Role on Reconsolidation and Persistence of Memories.

Back in 1968, Misanin and his group posited that reactivation of consolidated memories could support changes in that trace, similar to what might happen during the consolidation process. Not until 2000, when Nader et al. (2000) studied the behavioral effect of a protein synthesis inhibitor on retrieved memories, could this previous statement be taken under consideration once again; suggesting that consolidated memories can become labile after reactivation. The process of strengthening after memory labilization was named memory reconsolidation. In recent years, many studies pointed towards a critical participation of the extracellular signal-regulated kinase (ERK)/mitogen activated protein kinases (MAPKs) pathway in different memory processes (e.g., consolidation, extinction, reconsolidation, among others). In this review article, we will focus on how this system might be modulating the processes triggered after retrieval of well-consolidated memories in mice.

APP/Go protein Gßγ-complex signaling mediates Aß degeneration and cognitive impairment in Alzheimer's disease models.

Deposition of amyloid-ß (Aß), the proteolytic product of the amyloid precursor protein (APP), might cause neurodegeneration and cognitive decline in Alzheimer's disease (AD). However, the direct involvement of APP in the mechanism of Aß-induced degeneration in AD remains on debate. Here, we analyzed the interaction of APP with heterotrimeric Go protein in primary hippocampal cultures and found that Aß deposition dramatically enhanced APP-Go protein interaction in dystrophic neurites. APP overexpression rendered neurons vulnerable to Aß toxicity by a mechanism that required Go-Gßγ complex signaling and p38-mitogen-activated protein kinase activation. Gallein, a selective pharmacological inhibitor of Gßγ complex, inhibited Aß-induced dendritic and axonal dystrophy, abnormal tau phosphorylation, synaptic loss, and neuronal cell death in hippocampal neurons expressing endogenous protein levels. In the 3xTg-AD mice, intrahippocampal application of gallein reversed memory impairment associated with early Aß pathology. Our data provide further evidence for the involvement of APP/Go protein in Aß-induced degeneration and reveal that Gßγ complex is a signaling target potentially relevant for developing therapies for halting Aß degeneration in AD.