“Memory deterioration is a characteristic clinical symptom in patients with Alzheimer’s disease; however, the mechanisms underlying the memory loss are poorly understood. Here, [the authors] found that intraneuronal tau accumulation, the hallmark pathology seen in Alzheimer brains, induced a remarkable dephosphorylation/inactivation of nuclear cAMP response element binding protein (CREB), an important memory-associated protein. Further studies demonstrated that the abnormal tau accumulation could activate calcineurin, a calcium/calmodulin-dependent protein phosphatase and cause CREB dephosphorylation. Importantly, simultaneous inhibition of calcineurin remarkably attenuated tau-induced CREB inactivation and memory deficits. These findings not only reveal new mechanisms underlying Alzheimer memory deficits, but also provide a potential drug target for arresting tauopathies.”
Yin Y, Gao D, Wang Y, Wang ZH, Wang X, Ye J, Wu D, Fang L, Pi G, Yang Y, Wang XC, Lu C, Ye K, Wang JZ: Tau accumulation induces synaptic impairment and memory deficit by calcineurin-mediated inactivation of nuclear CaMKIV/CREB signaling. Proc. Natl. Acad. Sci USA 113(26): E3773-3781, 2016; doi: 10.1073/pnas.1604519113.