“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.”
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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.
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