Insulin, PKC signaling pathways and synaptic remodeling during memory storage and neuronal repair.
Protein kinase C (PKC) is involved in synaptic remodeling, induction of protein synthesis, and many other processes important in learning and memory. Activation of neuronal protein kinase C correlates with, and may be essential for, all phases of learning, including acquisition, consolidation, and reconsolidation. Protein kinase C activation is closely tied to hydrolysis of membrane lipids. Phospholipases C and A2 produce 1,2-diacylglycerol and arachidonic acid, which are direct activators of protein kinase C. Phospholipase C also produces inositol triphosphate, which releases calcium from internal stores. Protein kinase C interacts with many of the same pathways as insulin; therefore, it should not be surprising that insulin signaling and protein kinase C activation can both have powerful effects on memory storage and synaptic remodeling. However, investigating the possible roles of insulin in memory storage can be challenging, due to the powerful peripheral effects of insulin on glucose and the low concentration of insulin in the brain. Although peripheral for insulin, synthesized in the beta-cells of the pancreas, is primarily involved in regulating glucose, small amounts of insulin are also present in the brain. The functions of this brain insulin are inadequately understood. Protein kinase C may also contribute to insulin resistance by phosphorylating the insulin receptor substrates required for insulin signaling. Insulin is also responsible insulin-long term depression, a type of synaptic plasticity that is also dependent on protein kinase C. However, insulin can also activate PKC signaling pathways via PLC gamma, Erk 1/2 MAP kinase, and src stimulation. Taken together, the available evidence suggests that the major impact of protein kinase C and its interaction with insulin in the mature, fully differentiated nervous system appears to be to induce synaptogenesis, enhance memory, reduce Alzheimer's pathophysiology, and stimulate neurorepair.
Nelson
Thomas J
TJ
Blanchette Rockefeller Neurosciences Institute, 9601 Medical Center Drive, Rockville, Maryland 20850 USA.
Sun
Miao-Kun
MK
Hongpaisan
Jarin
J
Alkon
Daniel L
DL
D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D008568:Memory / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D009416:Nerve Regeneration; D009474:Neurons / Q000502:physiology*; D050722:Oncogene Protein v-cbl / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology*; D011972:Receptor, Insulin / Q000502:physiology; D015398:Signal Transduction; D020521:Stroke / Q000378:metabolism / Q000503:physiopathology; D013569:Synapses / Q000502:physiology*
D007328:Insulin; D050722:Oncogene Protein v-cbl; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases