The role of PKMζ in the maintenance of long-term memory: a review
| Autor: | Hamish Patel, Reza Zamani |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Memory Long-Term Dendritic spine Long-term memory General Neuroscience Long-Term Potentiation Long-term potentiation AMPA receptor Biology Hippocampus Mice 03 medical and health sciences Memory erasure 030104 developmental biology 0302 clinical medicine Memory Synapses Knockout mouse Animals Humans Memory impairment Protein kinase A Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Reviews in the Neurosciences. 32:481-494 |
| ISSN: | 2191-0200 0334-1763 |
| Popis: | Long-term memories are thought to be stored in neurones and synapses that undergo physical changes, such as long-term potentiation (LTP), and these changes can be maintained for long periods of time. A candidate enzyme for the maintenance of LTP is protein kinase M zeta (PKMζ), a constitutively active protein kinase C isoform that is elevated during LTP and long-term memory maintenance. This paper reviews the evidence and controversies surrounding the role of PKMζ in the maintenance of long-term memory. PKMζ maintains synaptic potentiation by preventing AMPA receptor endocytosis and promoting stabilisation of dendritic spine growth. Inhibition of PKMζ, with zeta-inhibitory peptide (ZIP), can reverse LTP and impair established long-term memories. However, a deficit of memory retrieval cannot be ruled out. Furthermore, ZIP, and in high enough doses the control peptide scrambled ZIP, was recently shown to be neurotoxic, which may explain some of the effects of ZIP on memory impairment. PKMζ knockout mice show normal learning and memory. However, this is likely due to compensation by protein-kinase C iota/lambda (PKCι/λ), which is normally responsible for induction of LTP. It is not clear how, or if, this compensatory mechanism is activated under normal conditions. Future research should utilise inducible PKMζ knockdown in adult rodents to investigate whether PKMζ maintains memory in specific parts of the brain, or if it represents a global memory maintenance molecule. These insights may inform future therapeutic targets for disorders of memory loss. |
| Databáze: | OpenAIRE |
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