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The key role of JNK in Alzheimer’s disease. Activation of JNK induces phosphorylation of the amyloid precursor protein (APP) at the Thr668 site, promoting the amyloidogenic proteolytic cleavage and the production of Aβ-toxic fragments in brain parenchyma. JIP-1, by linking the APP’s cytoplasmic tail, facilitates its phosphorylation by JNK. JNK also contributes to Tau hyper-phosphorylation and consequently to the formation of neurofibrillary tangles.
