Interaction between the guanylate kinase domain of PSD-95 and the proline-rich region and microtubule binding repeats 2 and 3 of tau.

The microtubule-associated protein tau is a key factor in neurodegenerative proteinopathies and is predominantly found in neuronal axons. However, somatodendritic localization of tau occurs in a subset of pathological and physiological tau. Dendritic tau can localize to post-synapses where it interacts with proteins of the post-synaptic density (PSD) protein PSD-95, a membrane-associated guanylate kinase (MAGUK) scaffold factor for organization of protein complexes within the PSD, to mediate downstream signals.

Reduction of advanced tau-mediated memory deficits by the MAP kinase p38γ.

Hyperphosphorylation of the neuronal tau protein contributes to Alzheimer's disease (AD) by promoting tau pathology and neuronal and cognitive deficits. In contrast, we have previously shown that site-specific tau phosphorylation can inhibit toxic signals induced by amyloid-β (Aβ) in mouse models. The post-synaptic mitogen-activated protein (MAP) kinase p38γ mediates this site-specific phosphorylation on tau at Threonine-205 (T205).