CaMKII mechanisms that promote pathological LTP impairments.

The Ca2+/calmodulin-dependent protein kinase II (CaMKII) is extremely abundant in the brain, where it prominently mediates hippocampal long-term potentiation (LTP), a form of synaptic plasticity thought to be required for learning and memory. However, CaMKII also mediates LTP impairments related to Alzheimer's disease (AD) and global cerebral ischemia (GCI), two conditions that are very distinct but are both associated with impairments in learning and memory. In both cases, CaMKII inhibitors prevented these LTP impairments. Thus, CaMKII actively mediates both physiological LTP and the pathological LTP impairments related to AD and GCI. Notably, these active LTP impairment mechanisms are in stark contrast to other conditions, like normal aging, where milder LTP impairments are caused instead by passive lack of CaMKII function.