Protein kinase M ζ and the maintenance of long-term memory

• PKMζ maintains long-term memory as it has persistent activity free from the second messengers without the N-terminal domain.
• Injection zeta inhibitory peptide (zeta inhibitory peptide, ZIP) to appropriate brain areas can inhibit relevant long-term memories.
• We found injection ZIP to insula could block morphine conditioned place preference in rhesus monkeys.

Although various molecules have been found to mediate the processes of memory acquisition and consolidation, the molecular mechanism to maintain memory still remains elusive. In recent years, a molecular pathway focusing on protein kinase Mζ (PKMζ) has become of interest to researchers because of its potential role in long-term memory maintenance. PKMζ is an isoform of protein kinase C (PKC) and has a related structure that influences its function in maintaining memory. Considerable evidence has been gathered on PKMζ activity, including loss of function studies using PKMζ inhibitors, such as PKMζ inhibitory peptide (ZIP), suggesting PKMζ plays an important role in long-term memory maintenance. This review provides an overview of the role of PKMζ in long-term memory and outlines the molecular structure of PKMζ, the molecular mechanism of PKMζ in long-term memory maintenance and future directions of PKMζ research.